Search results for: small cell carcinoma of rectum

Authors: Komal Vig

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Cardiovascular disease (CVD)-related deaths occur in 17.3 million people globally each year, accounting for 30% of all deaths worldwide, with a predicted annual incidence of deaths to reach 23.3 million globally by 2030. Autologous bypass grafts remain an important therapeutic option for the treatment of CVD, but the poor quality of the donor patient’s blood vessels, the invasiveness of the resection surgery, and postoperative movement restrictions create issues. The present study is aimed to improve the endothelialization of intimal surface of graft by using low temperature plasma (LTP) to increase the cell attachment and proliferation. Polytetrafluoroethylene (PTFE) was treated with LTP. Air was used as the feed-gas, and the pressure in the plasma chamber was kept at 800 mTorr. Scaffolds were also modified with gelatin and collagen by dipping method. Human umbilical vein endothelial cells (HUVEC) were plated on the developed scaffolds, and cell proliferation was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and by microscopy. mRNA expressions levels of different cell markers were investigated using quantitative real-time PCR (qPCR). XPS confirmed the introduction of oxygenated functionalities from LTP. HUVEC cells showed 80% seeding efficiency on the scaffold. Microscopic and MTT assays indicated increase in cell viability in LTP treated scaffolds, especially when treated with gelatin or collagen, compared to untreated scaffolds. Gene expression studies shows enhanced expression of cell adhesion marker Integrin- α 5 gene after LTP treatment. LTP treated scaffolds exhibited better cell proliferation and viability compared to untreated scaffolds. Protein treatment of scaffold increased cell proliferation. Based on our initial results, more scaffolds alternatives will be developed and investigated for cell growth and vascularization studies. Acknowledgments: This work is supported by the NSF EPSCoR RII-Track-1 Cooperative Agreement OIA-2148653.

Keywords: LTP, HUVEC cells, vascular graft, endothelialization

Procedia PDF Downloads 58

Authors: Hussain Mustatab Wahedi, Sun You Kim

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Skin acts as a barrier against the harmful environmental factors. Integrity and timely recovery of the skin from injuries and harmful effects of radiations is thus very important. This study aimed to investigate the importance of Sirt1 in the recovery of skin from UVB-induced damage and cutaneous wounds by using natural and synthetic novel Sirt1 activators. Juglone, known as a natural Pin1 inhibitor, and NED416 a novel synthetic Sirt1 activator were checked for their ability to regulate the expression and activity of Sirt1 and hence photo-damage and wound healing in cultured skin cells (NHDF and HaCaT cells) and mouse model by using Sirt1 siRNA knockdown, cell migration assay, GST-Pulldown assay, western blot analysis, tube formation assay, and immunohistochemistry. Interestingly, Sirt1 knockdown inhibited skin cell migration in vitro. Juglone up regulated the expression of Sirt1 in both the cell lines under normal and UVB irradiated conditions, enhanced Sirt1 activity and increased the cell viability by reducing reactive oxygen species synthesis and apoptosis. Juglone promoted wound healing by increasing cell migration and angiogenesis through Cdc42/Rac1/PAK, MAPKs and Smad pathways in skin cells. NED416 upregulated Sirt1 expression in HaCaT and NHDF cells as well as increased Sirt1 activity. NED416 promoted the process of wound healing in early as well as later stages by increasing macrophage recruitment, skin cell migration, and angiogenesis through Cdc42/Rac1 and MAPKs pathways. So, both these compounds activated Sirt1 and promoted the process of wound healing thus pointing towards the possible role of Sirt1 in skin regeneration and wound healing.

Keywords: skin regeneration, wound healing, Sirt1, UVB light

Procedia PDF Downloads 168

Authors: Rominkumar Busa, Shahira K. C., Lijiya A.

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Text recognition is an important area in computer vision which deals with detecting and recognising text from an image. The Optical Character Recognition (OCR) is a saturated area these days and with very good text recognition accuracy. However the same OCR methods when applied on text with small font sizes like the text data of chart images, the recognition rate is less than 30%. In this work, aims to extract small text in images using the deep learning model, CRNN with CTC loss. The text recognition accuracy is found to improve by applying image enhancement by super resolution prior to CRNN model. We also observe the text recognition rate further increases by 18% by applying the proposed method, which involves super resolution and character segmentation followed by CRNN with CTC loss. The efficiency of the proposed method shows that further pre-processing on chart image text and other small text images will improve the accuracy further, thereby helping text extraction from chart images.

Keywords: small text extraction, OCR, scene text recognition, CRNN

Procedia PDF Downloads 111

Authors: M. Riazat, H. Abdolvand, M. Baniassadi

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In this present work, 3D reconstruction of cathode of SOFC is developed with various volume fractions and porosity. Three Phase Boundary (TPB) of construction of such derived micro structures is calculated. The neural network is used to optimize the porosity and volume fraction of each phase to reach a structure with maximum TPB.

Keywords: fuel cell, solid oxide, TPB, 3D reconstruction

Procedia PDF Downloads 307

Authors: Mashayekh Amir Shahriar, Akhlaghi Morteza, Rajaee Hajar, Khani Mohammad Reza, Shokri Babak

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A new and novel approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper a pin-to-hole plasma jet suitable for biological applications is investigated, characterized and the possibility and feasibility of cancer cell treatment is evaluated. The characterization includes power consumption via Lissajous method, thermal behavior of plasma using Infra-red camera as a novel method, Optical Emission Spectroscopy (OES) to determine the species that are generated. Treatment of leukemia cancer cells is also implemented and MTT assay is used to evaluate viability.

Keywords: Atmospheric Pressure Plasma Jet (APPJ), Plasma Medicine, Cancer cell treatment, leukemia, Optical Emission

Procedia PDF Downloads 639

Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

Procedia PDF Downloads 308

Authors: Ismail Aksoy, Haci Bodur, Nihan Altintaş

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This paper introduces a boost converter with a new active snubber cell. In this circuit, all of the semiconductor components in the converter softly turns on and turns off with the help of the active snubber cell. Compared to the other converters, the proposed converter has advantages of size, number of components and cost. The main feature of proposed converter is that the extra voltage stresses do not occur on the main switches and main diodes. Also, the current stress on the main switch is acceptable level. Moreover, the proposed converter can operates under light load conditions and wide input line voltage. In this study, the operating principle of the proposed converter is presented and its operation is verified with the Proteus simulation software for a 1 kW and 100 kHz model.

Keywords: active snubber cell, boost converter, zero current switching, zero voltage switching

Procedia PDF Downloads 1014

Authors: Hassan Mahasneh, Abu Sesay

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We propose the use of relay terminals at the cell edge of an LTE-based cellar system. Each relay terminal is equipped with an omni-directional antenna. We refer to this scheme as the Omni-Relay (OR) scheme. The OR scheme coordinates the inter-cell interference (ICI) stemming from adjacent cells and increases the desired signal level at cell-edge regions. To validate the performance of the OR scheme, we derive the average signal-to-interference plus noise ratio (SINR) and the average capacity and compare it with the conventional universal frequency reuse factor (UFRF). The results show that the proposed OR scheme provides higher average SINR and average capacity compared to the UFRF due to the assistance of the distributed relay nodes.

Keywords: the UFRF scheme, the OR scheme, ICI, relay terminals, SINR, spectral efficiency

Procedia PDF Downloads 324

Authors: Abderrahmane Hemmani, Hamid Khachab, Dennai Benmoussa, Hassane Benslimane, Abderrachid Helmaoui

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Back surface field GaAs with n -p-p+ structures are found to have better characteristics than the conventional solar cells. A theory, based on the transport of both minority carriers under the charge neutrality condition, has been developed in the present paper which explains behavior of the back surface field solar cells. That is reported with an efficiency of 25,05% (Jsc=33.5mA/cm2, Vco=0.87v and fill factor 86% under AM1.5 global conditions). We present the effect of technological parameters of the p+ layer on the conversion efficiency on the solar cell. Good agreement is achieved between our results and the simulation results given the variation of the equivalent recombination velocity to p+ layer as a function of BSF thickness and BSF doping.

Keywords: back surface field, GaAs, solar cell, technological parameters

Procedia PDF Downloads 419

Authors: Fatima El Zahra Amin, Emine Efe

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This study was carried out to evaluate the effect of the education program for parents of children with Sickle Cell Anemia, on the knowledge level of parents and the reduction of pain relief by non-pharmacological methods used by parents at home. In Turkey, 54 parents and 109 from Chad agreed to participate in the survey. The data were collected by the researcher using a face-to-face interview method. Non-pharmacological treatment information form for parents, face expressions rating scale, and parent education program for non-pharmacological methods used in children with sickle cell anemia were used. It was determined that there was a statistically significant difference between the educational status, occupation, disease status, place of residence, family structure and age of parents of Chad and Turkey. According to the ratings of facial expressions scale, it was concluded that there was no significant difference between the children’s average degree of pain before and after administration of non-pharmacological methods by the groups of Chad and Turkey. It was determined that the educational programs prepared for parents of children with sickle cell anemia in both Turkey and Chad were effective in increasing the knowledge level of parents and also in reducing pain crisis with non-pharmacological methods parents used at home.

Keywords: Chad, child, non-pharmacological treatment methods, nurse, sickle cell anemia, Turkey

Procedia PDF Downloads 246

Authors: Noor Shafifiyaz Mohd Yazid, Najihah Mohd Hashim, Hapipah Mohd Ali, Syam Mohan, Rosea Go

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Artocarpus kemando is a plant species from Moraceae family. This plant is used as household utensil by the local and the fruits are edible. The plants’ bark was used for the extraction process and yielded the chloroform crude extract which was used to screen for anticancer potential. The cytotoxic effect of the extract on CAOV-3 and WRL 68 cell lines were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assays. Qualitative AO/PI assay was performed to confirm the apoptosis and necrosis process. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. In MTT assay, A. kemando inhibited 50% growth of CAOV-3 cells at 27.9 ± 0:03, 20.1± 0:03, 18.21± 0:04 µg/mL after 24, 48 and 72 hour, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with extract resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated A. kemando has potentially anticancer agent, particularly on human ovarian cancer.

Keywords: anticancer, Artocarpus kemando, ovarian cancer, cytotoxicity

Procedia PDF Downloads 537

Authors: Dina Fatmawati, Sofia Mubarika, Mae Sri Wahyuningsih

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Chemotherapy for breast cancer is largely ineffective, but innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. In our previous study, the combination of Doxorubicin (Dox) and ethanolic extract of Dioscorea esculenta tuber ((EED) was found to have a synergistic effect on T47D human breast cancer cell line. In this study, we investigated the apoptotic effect of the combination on T47D human breast cancer cells and normal fibroblasts cell line and its effects on the expression of Caspase-3 and cleaved poly (ADP-Ribose) Polymerase-1 (cPARP-1) protein. T47D cell lines and fibroblasts cells were treated with the combination of Dox and EED. Apoptotic effect of the combination was determined using flow cytrometry assay. Protein expressions were determined by immunocytochemistry staining. The percentage of apoptotic cells were significantly higher in T47D cell lines (75%) than that of in fibroblast cells (23%). The expression of Caspase 3 (84.53%) and cPARP-1 (83.36%) were significantly higher in the cancer cell lines than those of normal cells. These results indicate that the combination of doxorubicin and Dioscorea esculenta is a promising candidate for the treatment of breast cancer cells.

Keywords: Dioscorea esculenta, Doxorubicin, apoptosis, immunocytochemistry, cancer cells

Procedia PDF Downloads 436

Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

Procedia PDF Downloads 81

Authors: Abdoon A.S., El Ashkar E.A., Kandil O.M., Wael H. Eisa, Shaban A.M., Khaled H.M., El Ashkar M.R., El Shaer M., Hussein H., Shaalan A.H., El Sayed M.

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Cancer is a major obstacle to human health and development worldwide. Conventional strategies for cancer intervention include surgery, chemotherapy, and radiation therapy. Recently, plasmon photothermal therapy (PPTT) was introduced as a promising treatment for the management of cancer and several non-cancerous diseases that are generally characterized by overgrowth of abnormal cells. The present work was conducted to evaluate the cytotoxic efficacy and toxicity of gold nanorods (AuNRs) in dogs and cats suffering from spontaneous mammary gland. AuNRs was injected intratumoral (IT, n=10, dose of 75 p.p.m/kg body weight) or by using spray method after surgical removal of cancer tissue (n=2) in dogs and cats. Then exposed to laser light after 60 min. Treated animals were observed every 2 days and the morphological changes in tumor size and shape were recorded. Blood samples were collected before and after treatment for checking CBC, liver and kidney functions. Results revealed that AuNRs successfully treat mammary gland tumor in dogs and cats (adenocarcinoma type 1 to IV). AuNRs induced sloughing of carcinogenic tissue within 5 to 15 days. AuNRs have no toxic effect on blood profile and the toxicity studies still under evaluation. Conclusion, AuNRs can be used for treatment of mammary gland carcinoma in dogs and cats.

Keywords: pet animals, mammary gland tumor, AuNRs, photothermal therapy, toxicity studies

Procedia PDF Downloads 368

Authors: P. Thepnarintra, S. Nikorn

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Agricultural machinery industry plays an important role in the industrial development especially the production industry of the country. There has been continuing development responding to the higher demand of the production. However, the problem in agricultural machinery production still exists. Thus, the purpose of this research is to investigate problems on fundamental factors of industry based on the entrepreneurs’ point of view. The focus was on the small and medium size industry receiving a factory license typed number 0660 from the Department of Industrial Works. The investigation was on the comparison between the management of the small and medium size agricultural industry in 3 provinces in the central region of Thailand. Population in this study consisted of 189 company managers or managing directors, of which 101 were from the small size and 88 were from the medium size industry. The data were analyzed to find percentage, arithmetic mean, and standard deviation with independent sample T-test at the statistical significance .05. The results showed that the small and medium size agricultural machinery manufacturers in the central region of Thailand reported high problems in every aspect. When compared the problems on basic factors in running the business, it was found that there was no difference statistically at .05 in managing of the small and medium size agricultural machinery manufacturers. However, there was a statistically significant difference between the small and medium size agricultural machinery manufacturers on the aspect of policy and services of the government. The problems reported by the small and medium size agricultural machinery manufacturers were the services on public tap water and the problem on politic and stability of the country.

Keywords: agricultural machinery, manufacturers, problems, on running the business

Procedia PDF Downloads 272

Authors: Hanish Mohammed, C. H. Muthukumar Muthuchamy

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The advancement in the science and technology has made it possible to convert electrical energy into any desired form. It has given electrical energy a place of pride in the modern world. The survival of industrial undertakings and our social structure depends primarily upon low cost and uninterrupted supply of electrical energy. Microbial fuel cell (MFC) is a promising and emerging technique for sustainable bioelectricity generation and wastewater treatment. MFCs are devices which are capable of converting organic matter to electricity/hydrogen with help of microorganisms. Different kinds of wastewater could be used in this technique, distillery effluent is one of the most troublesome and complex and strong organic effluent with high chemical oxygen demand of 1,53,846 mg/L. A single cell MFC unit was designed and fabricated for the distillery effluent treatment and to generate electricity. Due to the high COD value of the distillery effluent helped in the production of energy for 74 days. The highest voltage got from the fuel cell is 206 mV on the 30th day. A maximum power density obtained from the MFC was 9.8 mW, treatment efficiency was evaluated in terms of COD removal and other parameters. COD removal efficiencies were around 68.5 % and other parameters such as Total Hardness (81.5%), turbidity (70 %), chloride (66%), phosphate (79.5%), Nitrate (77%) and sulphate (71%). MFC using distillery effluent is a promising new unexplored substrate for the power generation and sustainable treatment technique through harnessing of bioelectricity.

Keywords: microbial fuel cell (MFC), bioelectricity, distillery effluent, wastewater treatment

Procedia PDF Downloads 200

Authors: Omar Bendjimaa, Karzabi Abdelatif

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Small and medium enterprises have witnessed several developments in recent years thanks to the policies and programs of support given by the state, and that is due to their importance in local and national development. Nevertheless, the success and development of these firms depends on a number of factors, especially the human element, for instance, the culture of the manager has its origin in the culture of the community and is of crucial influence in these firms. In fact, this culture is nothing more than a set of values, perceptions, beliefs, symbols and practices repeated, in addition to the knowledge it has received from the readings and the modern means of education. All these factors have an impact on the effectiveness of governance, its resolutions, instructions and performance of its function as a manager of a medium or small enterprise is inevitably affected by these cultural values, it is the driving force, the leader, and the observer at the same time.

Keywords: small and medium enterprises, the culture of the manager, the culture of the community, values, perceptions, beliefs, symbols, performance

Procedia PDF Downloads 377

Authors: Khaled Shaaban

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Distracted driving, which includes anything that distracts a driver from the main task of driving, is one of the main causes of traffic accidents in modern societies. The objective of this research was to understand the type of activities that young drivers perform while driving in Qatar and to identify which activities cause the most distraction to the driver based on their experience. The data was collected through administered questionnaires in the city of Doha, Qatar. According to the participants, the majority reported that they use their cell phone all the time or occasionally while driving. Other significantly cited activities while driving included listening to music or radio, talking with passengers, and eating, drinking or smoking. When asked about the activities that distract the driver, using cell phone was listed as the most distracting activity followed by mental activities and adjusting GPS and audio device vehicle.

Keywords: driver distraction, young drivers, cell phone use, Qatar

Procedia PDF Downloads 475

Authors: L. Mallesha, P. Mallu, B. Veeresh

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In the present study, 2, 6-diflurobenzohydrazide and 4-fluorophenylisothiocyanate were used as the starting materials to synthesize 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3, 4-diamine. Further, compound 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3,4-diamine reacted with fluoro substituted benzaldehydes to yield a series of Schiff bases. All the final compounds were characterized using IR, 1H NMR, 13C NMR, MS and elemental analyses. New compounds were evaluated for their antiproliferative effect using the MTT assay method against four human cancer cell lines (K562, COLO-205, MDA-MB231, and IMR-32) for the time period of 24 h. Among the series, few compounds showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Schiff bases, MTT assay, antiproliferative activity, human cancer cell lines, 1, 2, 4-triazoles

Procedia PDF Downloads 353

Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour, Parisa Hasankhani Tehrani

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Background And Objective: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Shahid Ghazi Tabatabaei Hospital, Tabriz, Iran. Subjects And Methods: A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from March 2017 to march 2018. All consecutive patients admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. Results: During the study period, n=13 patients underwent a haematopoietic stem cell transplant. There were n=10 males and n=3 females. One patient was less than 15 years of age, while rests were adults. Median age±SD was 26.5±14.5 years (12∼54 years). The underlying diagnosis included Aplastic anemia (n=4), Thalassemia major (n=1), Multiple Myeloma (n=3), Acute leukemia (n=3), Hodgkin's lymphoma (n=1), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204, while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gr/dl. Conclusion: The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international criteria and pioneer country in BMT transplantation. Also, we hope that our blood consumption become less than it is now.

Keywords: blood consumption, C: T ratio, PRBCs, stem cell transplant, tabriz, Iran

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

Procedia PDF Downloads 52

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

Abstract:

Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Shivani Kuttuva, James Sampson, Timothy Simmons, Vinayak Thattaruparambil, Holly Burton, Peter Coyne

Abstract:

Anogenital mammary-like glands were established to be embryological remnants of breast tissue due to failed resolution of the ectodermal mammary ridge. However, recent studies are now considering this to represent normal constituents of the anogenital area with histological resemblance to the orthotopic breast tissue with multiple benign and malignant lesions arising from it. The incidence of the above has been predominant in females in the vulval region. Due to the paucity of cases reported in men, this poses a diagnostic and therapeutic challenge resulting in a delay in treatment and, thereby, poor outcomes. Our patient presented to the dermatology clinic with an itchy, purplish lesion in the peri-anal region which, on punch biopsy, was diagnosed to be Extra-mammary Paget’s disease and taken up for Wide local excision. Immunochemically, staining was positive for HER2, ER and Cytokeratin 7, keeping with the presence of actual breast tissue with no primary breast carcinoma. Due to the invasive nature of the disease, he required Abdominoperineal resection with flap reconstruction. Despite complete surgical clearance and adjuvant radiotherapy, the disease progressed to adjacent inguinal and obturator lymph nodes with origin resembling anogenital type mammary glands but histology negative for hormonal receptors of the breast.

Keywords: anogenital mammary-like glands, abdominoperineal resection, ectopic breast tissue, ectopic male breast carcinoma, peri-anal skin lesion

Procedia PDF Downloads 65

Authors: Agi Sunday

Abstract:

A descriptive analysis of reported cases of sickle cell disease and the level of awareness about genetic counselling in 30 hospitals were carried out. Additionally, 150 individuals between ages 16-45 were randomly selected for evaluation of genetic counselling awareness. The main tools for this study were questionnaires which were taken to hospitals, and individuals completed the others. The numbers of reported cases of sickle cell disease recorded in private, public and teaching hospitals were 14 and 57; 143 and 89; 272 and 57 for the periods of 1995-2000 and 2001-2005, respectively. A general informal genetic counselling took place mostly in the hospitals visited. 122 (86%) individuals had the knowledge of genetic disease and only 43 (30.3%) individuals have been exposed to genetic counselling. 64% of individuals agreed that genetic counselling would help in the prevention of genetic disease.

Keywords: sickle disease, genetic counseling, genetic testing, advocacy

Procedia PDF Downloads 372

Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

Abstract:

The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

Procedia PDF Downloads 377

Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

Abstract:

Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

Procedia PDF Downloads 292

Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

Abstract:

Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

Procedia PDF Downloads 319