Search results for: tumor segmentation

Authors: Sardorbek Numonov, Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Dongeun Choi, Byung-Woo Hong

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The detection of curvilinear structures often plays an important role in the analysis of images. In particular, it is considered as a crucial step for the diagnosis of chronic respiratory diseases to localize the fissures in chest CT imagery where the lung is divided into five lobes by the fissures that are characterized by linear features in appearance. However, the characteristic linear features for the fissures are often shown to be subtle due to the high intensity variability, pathological deformation or image noise involved in the imaging procedure, which leads to the uncertainty in the quantification of anatomical or functional properties of the lung. Thus, it is desired to enhance the linear features present in the chest CT images so that the distinctiveness in the delineation of the lobe is improved. We propose a recursive diffusion process that prefers coherent features based on the analysis of structure tensor in an anisotropic manner. The local image features associated with certain scales and directions can be characterized by the eigenanalysis of the structure tensor that is often regularized via isotropic diffusion filters. However, the isotropic diffusion filters involved in the computation of the structure tensor generally blur geometrically significant structure of the features leading to the degradation of the characteristic power in the feature space. Thus, it is required to take into consideration of local structure of the feature in scale and direction when computing the structure tensor. We apply an anisotropic diffusion in consideration of scale and direction of the features in the computation of the structure tensor that subsequently provides the geometrical structure of the features by its eigenanalysis that determines the shape of the anisotropic diffusion kernel. The recursive application of the anisotropic diffusion with the kernel the shape of which is derived from the structure tensor leading to the anisotropic scale-space where the geometrical features are preserved via the eigenanalysis of the structure tensor computed from the diffused image. The recursive interaction between the anisotropic diffusion based on the geometry-driven kernels and the computation of the structure tensor that determines the shape of the diffusion kernels yields a scale-space where geometrical properties of the image structure are effectively characterized. We apply our recursive anisotropic diffusion algorithm to the detection of curvilinear structure in the chest CT imagery where the fissures present curvilinear features and define the boundary of lobes. It is shown that our algorithm yields precise detection of the fissures while overcoming the subtlety in defining the characteristic linear features. The quantitative evaluation demonstrates the robustness and effectiveness of the proposed algorithm for the detection of fissures in the chest CT in terms of the false positive and the true positive measures. The receiver operating characteristic curves indicate the potential of our algorithm as a segmentation tool in the clinical environment. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: anisotropic diffusion, chest CT imagery, chronic respiratory disease, curvilinear structure, fissure detection, structure tensor

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Angel Champion

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Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

Procedia PDF Downloads 126

Authors: Abdelkader Soumaya, Aymen Arfaoui, Noureddine Ben Ayed, Ali Kadri

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The Chotts belt represents the southernmost folded structure in the Tunisian Atlas domain. It is dominated by inherited deep extensional E-W trending fault zones, which are reactivated as strike-slip faults during the Cenozoic compression. By examining the geological maps at different scales and based on the fieldwork data, we propose new structural interpretations for the geometries and fault kinematics in the Chotts chain. A set of ENE-WSW right-lateral en echelon folds, with curved shapes and steeply inclined southern limbs, is visible in the map view of this belt. These asymmetric tight anticlines are affected by E-W trending fault segments linked by local bends and stepovers. The revealed kinematic indicators along one of these E-W striated faults (Tafferna segment), such as breccias and gently inclined slickenlines (N094, 80N, 15°W pitch angles), show direct evidence of dextral strike-slip movement. The calculated stress tensors from corresponding faults slip data reveal an overall strike-slip tectonic regime with reverse component and NW-trending sub-horizontal σ1 axis ranking between N130 to N150. From west to east, we distinguished several types of structures along the segmented dextral fault system of the Chotts Range. The NE-SW striking fold-thrust belt (~25 km-long) between two continuously linked E-W fault segments (NW of Tozeur town) has been suggested as a local restraining bend. The central part of the Chotts chain is occupied by the ENE-striking Ksar Asker anticlines (Taferna, Torrich, and Sif Laham), which are truncated by a set of E-W strike-slip fault segments. Further east, the fault segments of Hachichina and Sif Laham connected across the NW-verging asymmetric fold-thrust system of Bir Oum Ali, which can be interpreted as a left-stepping contractional bend (~20 km-long). The oriental part of the Chotts belt corresponds to an array of subparallel E-W oriented fault segments (i.e., Beidha, Bouloufa, El Haidoudi-Zemlet El Beidha) with similar lengths (around 10 km). Each of these individual separated segments is associated with curved ENE-trending en echelon right-stepping anticlines. These folds are affected by a set of conjugate R and R′ shear-type faults indicating a dextral strike-lip motion. In addition, the relay zones between these E-W overstepping fault segments define local releasing stepovers dominated by NW-SE subsidiary faults. Finally, the Chotts chain provides well-exposed examples of strike-slip tectonics along E-W distributed fault segments. Each fault zone shows a typical strike-slip architecture, including parallel fault segments connecting via local stepovers or bends. Our new structural interpretations for this region reveal a great influence of the E-W deep fault segments on regional tectonic deformations and stress field during the Cenozoic shortening.

Keywords: chotts belt, tunisian atlas, strike-slip fault, stepovers, fault segments

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Aymen Arfaoui, Abdelkader Soumaya, Noureddine Ben Ayed

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The study region is located in the Tunisian Dorsal Backland (Central Mediterranean), which is the easternmost part of the Saharan Atlas mountain range, trending southwest-northeast. Based on our fieldwork, seismic tomography images, seismicity, and previous studies, we propose an interpretation of the relationship between the surface deformation and fault kinematics in the study area and the internal dynamic processes acting in the Central Mediterranean from the Cenozoic to the present. The subduction and dynamics of internal forces beneath the complicated Maghrebides mobile belt have an impact on the Tertiary and Quaternary tectonic regimes in the Pelagian and Atlassic foreland that is part of our study region. The left lateral reactivation of the major "Tunisian N-S Axis fault" and the development of a compressional relay between the Hammamet Korbous and Messella-Ressas faults are possibly a result of tectonic stresses due to the slab roll-back following the Africa/Eurasia convergence. After the slab segmentation and its eastward migration (5–4 Ma) and the formation of the Strait of Sicily "rift zone" further east, a transtensional tectonic regime has been installed in this area. According to seismic tomography images, the STEP fault of the "North-South Axis" at Hammamet-Korbous coincides with the western edge of the "Slab windows" of the Sicilian Channel and the eastern boundary of the positive anomalies attributed to the residual Slab of Tunisia. On the other hand, significant E-W Plio-Quaternary tectonic activity may be observed along the eastern portion of this STEP fault system in the Grombalia zone as a result of recent vertical lithospheric motion in response to the lateral slab migration eastward to Sicily Channel. According to SKS fast splitting directions, the upper mantle flow pattern beneath Tunisian Dorsal is parallel to the NE-SW to E-W orientation of the Shmin identified in the study area, similar to the Plio-Quaternary extensional orientation in the Central Mediterranean. Additionally, the removal of the lithosphere and the subsequent uplift of the sub-lithospheric mantle beneath the topographic highs of the Dorsal and its surroundings may be the cause of the dominant extensional to transtensional Quaternary regime. The occurrence of strike-slip and extensional seismic events in the Pelagian block reveals that the regional transtensional tectonic regime persists today. Finally, we believe that the geodynamic history of the study area since the Cenozoic is primarily influenced by the preexisting weak zones, the African slab detachment, and the upper mantle flow pattern in the central Mediterranean.

Keywords: Tunisia, lithospheric discontinuity (STEP fault), geodynamic evolution, Tunisian dorsal backland, strike-slip fault, seismic tomography, seismicity, central Mediterranean

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Farah Amalina Mohamed Affandi, Redhwan Ahmad Al-Naggar, Seok Mui Wang, Thanikasalam Kathiresan

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Gestational choriocarcinoma is a condition in which there is an abnormal growth or a tumor inside the women’s uterus after conception. It is a type of gestational trophoblastic disease which is relatively rare and malignant. The current epidemiological data of this disease are inadequate. The purposes of this study are to examine the epidemiology of choriocarcinoma and their risk factors based on all available population-based and hospital-based data of the disease. In this study, we searched The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases using the keywords ‘choriocarcinoma’, ‘gestational’, ‘gestational choriocarcinoma’ and ‘epidemiology’. We included only human studies published in English between 1995 and 2015 to ensure up to date evidence. Case studies, case reports, animal studies, letters to the editor, news, and review articles were excluded. Retrieved articles were screened in three phases. In the first phase, any articles that did not match the inclusion criteria based solely on titles were excluded. In the second phase, the abstracts of remaining articles were screened thoroughly; any articles that did not meet our inclusion criteria were excluded. In the final phase, full texts of the remaining articles were read and assessed to exclude articles that did not meet the inclusion criteria or any articles that fulfilled the exclusion criteria. Duplicates articles were also removed. Systematic reviews and meta-analysis were excluded. Extracted data were summarized in table and figures descriptively. The reference lists of included studies were thoroughly reviewed in search for other relevant studies. A total of ten studies met all the selection criteria. Nine were retrospective studies and one was cohort study. Total numbers of 4563 cases of choriocarcinoma were reviewed from several countries which are Korea, Japan, South Africa, USA, New Mexico, Finland, Turkey, China, Brazil and The Netherlands. Different studies included different range of age with their mean age of 28.5 to 30.0 years. All studies investigated on the disease’s incidence rate, only two studies examined on the risk factors or associations of the disease. Approximately 20% of the studies showed a reduction in the incidence of choriocarcinoma while the other 80% showed inconsistencies in rate. Associations of age, fertility age, occupations and socio-demographic with the status remains unclear. There is limited information on the epidemiological aspects of gestational choriocarcinoma. The observed results indicated there was a decrease in the incidence rate of gestational choriocarcinoma globally. These could be due to the reduction in the incidence of molar pregnancy and the efficacy of the treatment, mainly by chemotherapy.

Keywords: epidemiology, gestational choriocarcinoma, incidence, prevalence, risk factor

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Authors: Maximilian Engelhardt, Stephan Seeck

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The COVID-19 pandemic is accelerating the already growing field of e-commerce. The resulting urban freight transport volume leads to traffic and negative environmental impact. Furthermore, the service level of parcel logistics service provider is lacking far behind the expectations of consumer. These challenges can be solved by radically reorganize the urban last mile distribution structure: parcels could be consolidated in a micro hub within the inner city and delivered within time windows by cargo bike. This approach leads to a significant improvement of consumer satisfaction with their overall delivery experience. However, this approach also leads to significantly increased costs per parcel. While there is a relevant share of online shoppers that are willing to pay for such a delivery service there are no deeper insights about this target group available in the literature. Being aware of the importance of knowing target groups for businesses, the aim of this paper is to elaborate the most important factors that determine the willingness to pay for sustainable and service-oriented parcel delivery (factor analysis) and to derive customer segments (cluster analysis). In order to answer those questions, a data set is analyzed using quantitative methods of multivariate statistics. The data set was generated via an online survey in September and October 2020 within the five largest cities in Germany (n = 1.071). The data set contains socio-demographic, living-related and value-related variables, e.g. age, income, city, living situation and willingness to pay. In a prior work of the author, the data was analyzed applying descriptive and inference statistical methods that only provided limited insights regarding the above-mentioned research questions. The analysis in an exploratory way using factor and cluster analysis promise deeper insights of relevant influencing factors and segments for user behavior of the mentioned parcel delivery concept. The analysis model is built and implemented with help of the statistical software language R. The data analysis is currently performed and will be completed in December 2021. It is expected that the results will show the most relevant factors that are determining user behavior of sustainable and service-oriented parcel deliveries (e.g. age, current service experience, willingness to pay) and give deeper insights in characteristics that describe the segments that are more or less willing to pay for a better parcel delivery service. Based on the expected results, relevant implications and conclusions can be derived for startups that are about to change the way parcels are delivered: more customer-orientated by time window-delivery and parcel consolidation, more environmental-friendly by cargo bike. The results will give detailed insights regarding their target groups of parcel recipients. Further research can be conducted by exploring alternative revenue models (beyond the parcel recipient) that could compensate the additional costs, e.g. online-shops that increase their service-level or municipalities that reduce traffic on their streets.

Keywords: customer segmentation, e-commerce, last mile delivery, parcel service, urban logistics, willingness-to-pay

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Authors: Grace C. Kuroki, Yixin Hu, Bailey Surtees, Rebecca Krimins, Nicholas J. Durr, Dara L. Kraitchman

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The purpose of this study was to perform a Phase I veterinary clinical trial with a low-cost, carbon-dioxide-based, passive thaw cryoablation device as proof-of-principle for application in pets and translation to third-world treatment of breast cancer. This study was approved by the institutional animal care and use committee. Client-owned dogs with subcutaneous masses, primarily lipomas or mammary cancers, were recruited for the study. Inclusion was based on clinical history, lesion location, preanesthetic blood work, and fine needle aspirate or biopsy confirmation of mass. Informed consent was obtained from the owners for dogs that met inclusion criteria. Ultrasound assessment of mass extent was performed immediately prior to mass cryoablation. Dogs were placed under general anesthesia and sterilely prepared. A stab incision was created to insert a custom 4.19 OD x 55.9 mm length cryoablation probe (Kubanda Cryotherapy) into the mass. Originally designed for treating breast cancer in low resource settings, this device has demonstrated potential in effectively necrosing subcutaneous masses. A dose escalation study of increasing freeze-thaw cycles (5/4/5, 7/5/7, and 10/7/10 min) was performed to assess the size of the iceball/necrotic extent of cryoablation. Each dog was allowed to recover for ~1-2 weeks before surgical removal of the mass. A single mass was treated in seven dogs (2 mammary masses, a sarcoma, 4 lipomas, and 1 adnexal mass) with most masses exceeding 2 cm in any dimension. Mass involution was most evident in the malignant mammary and adnexal mass. Lipomas showed minimal shrinkage prior to surgical removal, but an area of necrosis was evident along the cryoablation probe path. Gross assessment indicated a clear margin of cryoablation along the cryoprobe independent of tumor type. Detailed histopathology is pending, but complete involution of large lipomas appeared to be unlikely with a 10/7/10 protocol. The low-cost, carbon dioxide-based cryotherapy device permits a minimally invasive technique that may be useful for veterinary applications but is also informative of the unlikely resolution of benign adipose breast masses that may be encountered in third world countries.

Keywords: cryoablation, cryotherapy, interventional oncology, veterinary technology

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Authors: Vangmayee. V. Subban, Somashekara H. S, Shwetha Prabhu, Jayashree S. Bhat

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Introduction and Need: Phonological processing is critical in learning to read alphabetical and non-alphabetical languages. However, its role in learning to read Kannada an alphasyllabary is equivocal. The literature has focused on the developmental role of phonological awareness on reading. To the best of authors knowledge, the role of phonological memory and phonological naming has not been addressed in alphasyllabary Kannada language. Therefore, there is a need to evaluate the comprehensive role of the phonological processing skills in Kannada on word decoding skills during the early years of schooling. Aim and Objectives: The present study aimed to explore the phonological processing abilities and their role in learning to decode pseudowords in children learning to read the Kannada language during initial years of formal schooling between 5.6 to 8.6 years. Method: In this cross sectional study, 60 typically developing Kannada speaking children, 20 each from Grade I, Grade II, and Grade III between the age range of 5.6 to 6.6 years, 6.7 to 7.6 years and 7.7 to 8.6 years respectively were selected from Kannada medium schools. Phonological processing abilities were assessed using an assessment tool specifically developed to address the objectives of the present research. The assessment tool was content validated by subject experts and had good inter and intra-subject reliability. Phonological awareness was assessed at syllable level using syllable segmentation, blending, and syllable stripping at initial, medial and final position. Phonological memory was assessed using pseudoword repetition task and phonological naming was assessed using rapid automatized naming of objects. Both phonological awareneness and phonological memory measures were scored for the accuracy of the response, whereas Rapid Automatized Naming (RAN) was scored for total naming speed. Results: The mean scores comparison using one-way ANOVA revealed a significant difference (p ≤ 0.05) between the groups on all the measures of phonological awareness, pseudoword repetition, rapid automatized naming, and pseudoword reading. Subsequent post-hoc grade wise comparison using Bonferroni test revealed significant differences (p ≤ 0.05) between each of the grades for all the tasks except (p ≥ 0.05) for syllable blending, syllable stripping, and pseudoword repetition between Grade II and Grade III. The Pearson correlations revealed a highly significant positive correlation (p=0.000) between all the variables except phonological naming which had significant negative correlations. However, the correlation co-efficient was higher for phonological awareness measures compared to others. Hence, phonological awareness was chosen a first independent variable to enter in the hierarchical regression equation followed by rapid automatized naming and finally, pseudoword repetition. The regression analysis revealed syllable awareness as a single most significant predictor of pseudoword reading by explaining the unique variance of 74% and there was no significant change in R² when RAN and pseudoword repetition were added subsequently to the regression equation. Conclusion: Present study concluded that syllable awareness matures completely by Grade II, whereas the phonological memory and phonological naming continue to develop beyond Grade III. Amongst phonological processing skills, phonological awareness, especially syllable awareness is crucial for word decoding than phonological memory and naming during initial years of schooling.

Keywords: phonological awareness, phonological memory, phonological naming, phonological processing, pseudo-word decoding

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Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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Authors: Meral Huri, Sedef Şahin

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Post-traumatic stress disorder (PTSD) is characterized by psychiatric symptoms and triggered by a terrifying experience which may immediately effect cognitive, affective, behavioral and social skills of the individual. One of the most common noncutaneous cancer among men is prostate cancer. The incidence of psychological stress is quite common in men with prostate cancer. The aim of the study was to explore the PTSD frequency among prostate cancer and define the relationship between occupational participation, coping skills and level of perceived social support among patients with prostate cancer. Forty patients diagnosed with prostate cancer were included in the study. After dividing the patients into two groups ( study/ control) according to type of tumor, we recorded their characteristics and evaluations differences. We evaluated the demographic information form, Structured Clinical Interview for DSM-IV (SCID- I)- Clinical Version for PTSD, Multidimensional Scale of Perceived Social Support, Styles of Coping Inventory and Canadian Occupational Performance Measure (COPM) before and after 1 month from surgery. The mean age of the study group (n:18) was 65.85.6 years (range: 61-79 years). The mean age of the control group (n: 22) was a little bit higher than the study group with mean age 71.3±6.9 years (range: 60-85 years). There was no statistically significant difference between the groups for age and the other characteristics. According to the results of the study, statistically significant difference was found between the level of PTSD of study and the control group. 22% of study group showed PTSD while 13% of the control group showed PTSD (r: 0.02, p<0.001). The scores of study group and control group showed statistically significant difference in five sub-categories of Styles of Coping Inventory. Patients with prostate cancer showed decreased scores in optimistic, seeking social supports and self-confident approach, while increased scores in helpless and submissive sub-categories than the control group (p<0.001). The scores of Multidimensional Scale of Perceived Social Supports of study group and control group showed statistically significant difference. The total perceived social supports score of the study group was 71.34 ± 0.75 while it was 75.34 ± 0.64 for the control group. Total and the sub-category scores of study group were statistically significant lower than the control group. According to COPM, mean scores of occupational participation of study group for occupational performance were 4.32±2.24 and 7.01±1.52 for the control group, respectively). Mean Satisfaction scores were 3,22±2.31 and 7.45±1.74 for the study and control group, respectively. The patients with prostate cancer and benign prostate hyperplasia (BPH) did not show any statistically difference in activity performance (r:0.87) while patients with prostate cancer showed statistically lower scores than the patients with BPH in activity satisfaction (r:0.02, p<0.001).Psycho-social occupational therapy interventions might help to decrease the prevalence of PTSD by increasing associated factors such as the social support perception, using coping skills and activity participation of patients with prostate cancer.

Keywords: activity performance, occupational therapy, posttraumatic stress disorder, prostate cancer

Procedia PDF Downloads 127

Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Ja-Keoung Koo, Kensuke Nakamura, Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Byung-Woo Hong

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The machine learning techniques based on a convolutional neural network (CNN) have been actively developed and successfully applied to a variety of image analysis tasks including reconstruction, noise reduction, resolution enhancement, segmentation, motion estimation, object recognition. The classical visual information processing that ranges from low level tasks to high level ones has been widely developed in the deep learning framework. It is generally considered as a challenging problem to derive visual interpretation from high dimensional imagery data. A CNN is a class of feed-forward artificial neural network that usually consists of deep layers the connections of which are established by a series of non-linear operations. The CNN architecture is known to be shift invariant due to its shared weights and translation invariance characteristics. However, it is often computationally intractable to optimize the network in particular with a large number of convolution layers due to a large number of unknowns to be optimized with respect to the training set that is generally required to be large enough to effectively generalize the model under consideration. It is also necessary to limit the size of convolution kernels due to the computational expense despite of the recent development of effective parallel processing machinery, which leads to the use of the constantly small size of the convolution kernels throughout the deep CNN architecture. However, it is often desired to consider different scales in the analysis of visual features at different layers in the network. Thus, we propose a CNN model where different sizes of the convolution kernels are applied at each layer based on the random projection. We apply random filters with varying sizes and associate the filter responses with scalar weights that correspond to the standard deviation of the random filters. We are allowed to use large number of random filters with the cost of one scalar unknown for each filter. The computational cost in the back-propagation procedure does not increase with the larger size of the filters even though the additional computational cost is required in the computation of convolution in the feed-forward procedure. The use of random kernels with varying sizes allows to effectively analyze image features at multiple scales leading to a better generalization. The robustness and effectiveness of the proposed CNN based on random kernels are demonstrated by numerical experiments where the quantitative comparison of the well-known CNN architectures and our models that simply replace the convolution kernels with the random filters is performed. The experimental results indicate that our model achieves better performance with less number of unknown weights. The proposed algorithm has a high potential in the application of a variety of visual tasks based on the CNN framework. Acknowledgement—This work was supported by the MISP (Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by IITP, and NRF-2014R1A2A1A11051941, NRF2017R1A2B4006023.

Keywords: deep learning, convolutional neural network, random kernel, random projection, dimensionality reduction, object recognition

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Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

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Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

Procedia PDF Downloads 244

Authors: Scott M. Black, Craig Maclean, Pauline Hall Barrientos, Konstantinos Ritos, Asimina Kazakidi

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Aortic aneurysms and dissections are leading causes of death in cardiovascular disease. Both inevitably lead to hemodynamic instability without surgical intervention in the form of vascular stent-graft deployment. An accurate description of the aortic geometry and blood flow in patient-specific cases is vital for treatment planning and long-term success of such grafts, as they must generate physiological branch perfusion and in-stent hemodynamics. The aim of this study was to create patient-specific computational fluid dynamics (CFD) models through a multi-modality, multi-dimensional approach with boundary condition optimization to predict branch flow rates and in-stent hemodynamics in custom stent-graft configurations. Three-dimensional (3D) thoracoabdominal aortae were reconstructed from four-dimensional flow-magnetic resonance imaging (4D Flow-MRI) and computed tomography (CT) medical images. The former employed a novel approach to generate and enhance vessel lumen contrast via through-plane velocity at discrete, user defined cardiac time steps post-hoc. To produce patient-specific boundary conditions (BCs), the aortic geometry was reduced to a one-dimensional (1D) model. Thereafter, a zero-dimensional (0D) 3-Element Windkessel model (3EWM) was coupled to each terminal branch to represent the distal vasculature. In this coupled 0D-1D model, the 3EWM parameters were optimized to yield branch flow waveforms which are representative of the 4D Flow-MRI-derived in-vivo data. Thereafter, a 0D-3D CFD model was created, utilizing the optimized 3EWM BCs and a 4D Flow-MRI-obtained inlet velocity profile. A sensitivity analysis on the effects of stent-graft configuration and BC parameters was then undertaken using multiple stent-graft configurations and a range of distal vasculature conditions. 4D Flow-MRI granted unparalleled visualization of blood flow throughout the cardiac cycle in both the pre- and postsurgical states. Segmentation and reconstruction of healthy and stented regions from retrospective 4D Flow-MRI images also generated 3D models with geometries which were successfully validated against their CT-derived counterparts. 0D-1D coupling efficiently captured branch flow and pressure waveforms, while 0D-3D models also enabled 3D flow visualization and quantification of clinically relevant hemodynamic parameters for in-stent thrombosis and graft limb occlusion. It was apparent that changes in 3EWM BC parameters had a pronounced effect on perfusion distribution and near-wall hemodynamics. Results show that the 3EWM parameters could be iteratively changed to simulate a range of graft limb diameters and distal vasculature conditions for a given stent-graft to determine the optimal configuration prior to surgery. To conclude, this study outlined a methodology to aid in the prediction post-surgical branch perfusion and in-stent hemodynamics in patient specific cases for the implementation of custom stent-grafts.

Keywords: 4D flow-MRI, computational fluid dynamics, vascular stent-grafts, windkessel

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

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Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

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Authors: Samil Ozcan

Abstract:

Airlines companies target different customer segments in consideration of pricing, service quality, flight network, etc. and their brand positioning accords with the marketization strategies developed in the same direction. The object of this study, Turkish Airlines, has many peculiarities regarding its brand positioning as compared to its rivals in the sector. In the first place, it appeals to a global customer group because of its Star Alliance membership and its broad flight network with 315 destination points. The second group in its customer segmentation includes domestic customers. For this group, the company follows a marketing strategy that plays to local culture and accentuates the image of Turkishness as an emotional allurement. The advertisements and publicity projects designed in this regard put little emphasis on the service quality the company offers to its clients; it addresses the emotions of the consumers rather than individual benefits and relies on the historical memory of the nation and shared cultural values. This study examines the publicity work which aims at the second segment customer group focusing on Turkish Airlines’ 85th Anniversary Commercial through a symbolic meaning analysis approach. The commercial presents six stories with undertones of nationalism in its theme. Nationalism is not just the product of collective interests based on reason but a result of patriotism in the sense of loyalty to state and nation and love of ethnic belonging. While nationalism refers to concrete notions such as blood tie, common ancestor, shared history, it is not the actuality of these notions that it draws its real strength but the emotions invested in them. The myths of origin, the idea of common homeland, boundary definitions, and symbolic acculturation have instrumental importance in the development of these commonalities. The commercial offers concrete examples for an analysis of Connor’s definition of nationalism based on emotions. Turning points in the history of the Turkish Republic and the historical mission Turkish Airlines undertook in these moments are narrated in six stories in the commercial with a highly emotional theme. These emotions, in general, depend on collective memory generated by national consciousness. Collective memory is not simply remembering the past. It is constructed through the reconstruction and reinterpretation of the past in the present moment. This study inquires the motivations behind the nationalist emotions generated within the collective memory by engaging with the commercial released for the 85th anniversary of Turkish Airlines as the object of analysis. Symbols and myths can be read as key concepts that reveal the relation between 'identity and memory'. Because myths and symbols do not merely reflect on collective memory, they reconstruct it as well. In this sense, the theme of the commercial defines the image of Turkishness with virtues such as self-sacrifice, helpfulness, humanity, and courage through a process of meaning creation based on symbolic mythologizations like flag and homeland. These virtues go beyond describing the image of Turkishness and become an instrument that defines and gives meaning to Turkish identity.

Keywords: collective memory, emotions, identity, nationalism

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

Abstract:

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

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

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Authors: Ahmed Abdallatif

Abstract:

Background: Patients with malignant germ cell tumors have age distribution in two peaks, with the first one during infancy and the second after the onset of puberty. Gonadal germ cell tumors are the most common malignant ovarian tumor in females aged below twenty years. Sacrococcygeal and retroperitoneal abdominal tumors usually presents in a large size before the onset of symptoms. Methods: Patients with pediatric germ cell tumors presenting to Children’s Cancer Hospital Egypt and National Cancer Institute Egypt from January 2008 to June 2011 Patients underwent stratification according to risk into low, intermediate and high risk groups according to children oncology group classification. Objectives: Assessment of the clinicopathologic features of all cases of pediatric germ cell tumors and classification of malignant cases according to their stage, and the primary site to low, intermediate and high risk patients. Evaluation of surgical management in each group of patients focusing on surgical approach, the extent of surgical resection according to each site, ability to achieve complete surgical resection and perioperative complications. Finally, determination of the three years overall and disease-free survival in different groups and the relation to different prognostic factors including the extent of surgical resection. Results: Out of 131 cases surgically explored only 26 cases had re exploration with 8 cases explored for residual disease 9 cases for remote recurrence or metastatic disease and the other 9 cases for other complications. Patients with low risk kept under follow up after surgery, out of those of low risk group (48 patients) only 8 patients (16.5%) shifted to intermediate risk. There were 20 patients (14.6%) diagnosed as intermediate risk received 3 cycles of compressed (Cisplatin, Etoposide and Bleomycin) and all high risk group patients 69patients (50.4%) received chemotherapy. Stage of disease was strongly and significantly related to overall survival with a poorer survival in late stages (stage IV) as compared to earlier stages. Conclusion: Overall survival rate at 3 three years was (76.7% ± 5.4, 3) years EFS was (77.8 % ±4.0), however 3 years DFS was much better (89.8 ± 3.4) in whole study group with ovarian tumors had significantly higher Overall survival (90% ± 5.1). Event Free Survival analysis showed that Male gender was 3 times likely to have bad events than females. Patients who underwent incomplete resection were 4 times more than patients with complete resection to have bad events. Disease free survival analysis showed that Patients who underwent incomplete surgery were 18.8 times liable for recurrence compared to those who underwent complete surgery, and patients who were exposed to re-excision were 21 times more prone to recurrence compared to other patients.

Keywords: extragonadal, germ cell tumors, gonadal, pediatric

Procedia PDF Downloads 198

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

Abstract:

Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

Procedia PDF Downloads 152