Search results for: breast cancer cell lines

Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

Abstract:

Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

Abstract:

Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

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Authors: Charalampos Saridakis, Stelios Tsafarakis

Abstract:

Although environmental concern is on the rise across Europe, current market data indicate that adoption rates of environmentally friendly vehicles remain extremely low. Against this background, the aim of this paper is to a) assess preferences of European consumers for clean-fuel cars and their characteristics and b) design car lines that optimize the combination of fuel types among models in the line-up. In this direction, the authors introduce a new evolutionary mechanism and implement it to stated-preference data derived from a large-scale choice-based conjoint experiment that measures consumer preferences for various factors affecting clean-fuel vehicle (CFV) adoption. The proposed two-step methodology provides interesting insights into how new and existing fuel-types can be combined in a car line that maximizes customer satisfaction.

Keywords: clean-fuel vehicles, product line design, conjoint analysis, choice experiment, differential evolution

Procedia PDF Downloads 252

Authors: Mohammad Kousara, Françoise Dumas, Rama Ibrahim, Joëlle Dubois, Joël Raingeaud

Abstract:

Suberosanes are a small group of marine natural sesquiterpenes discovered since 1996 by Boyd, Sheu and Qi from three gorgonians. Their skeleton was previously found in quadranes produced by the terrestrial fungus Aspergillus terreus. Up to date, eleven suberosanes are described from which (-)-suberosanone and (-)-suberosenol A are reaching the picomolar cytotoxicity level on human solid tumors cell lines. Due to their impressive cytotoxic properties and their limited availability, we undertook an asymmetric synthesis of the most active members of this family in order to get insight into their absolute configurations and their biological properties. The challenge of their synthesis is the regio- and stereoselective elaboration of the compact bridged tricyclic skeleton with up to five all adjacent asymmetric centers, including a central quaternary carbon one. Our strategy is based on an aza-ene-synthesis key step which is regio-and stereo-controlled by the choice of a chiral amine enantiomer. it approach is concise and flexible, the enantiopur ABC tricyclic intermediate that have been synthesized being the common precursor of suberosanes.

Keywords: suberosanes, asymmetric synthesis, sesquiterpenes, quadranes

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Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

Abstract:

Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

Abstract:

Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: Laila H. Abdel-Rahman, Mohamed Shaker S. Adam, Ahmed M. Abu-Dief, Hanan El-Sayed Ahmed

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In this investigation, Cu(II), Pd(II) and Ag(I) complexes with the tetra-dentate DSPH Schiff base ligand were synthesized. The DSPH Schiff base and its complexes were characterized by using different physicochemical and spectral analysis. The results revealed that the metal ions coordinated with DSPH ligand through azomethine nitrogen and phenolic oxygen. Cu(II), Pd(II) and Ag(I) complexes are present in a 1:1 molar ratio. Pd(II) and Ag(I) complexes have square planar geometries while, Cu(II) has a distorted octahedral (Oh) geometry. All investigated complexes are nonelectrolytes. The investigated compounds were tested against different strains of bacteria and fungi. Both prepared compounds showed good results of inhibition against the selected pathogenic microorganism. Moreover, the interaction of investigated complexes with CT-DNA was studied via various techniques and the binding modes are mainly intercalative and grooving modes. Operating Environment MOE package was used to do docking studies for the investigated complexes to explore the potential binding mode and energy. Furthermore, the growth inhibitory effect of the investigated compounds was examined on some cancer cells lines.

Keywords: tetradentate, antimicrobial, CT-DNA interaction, docking, anticancer

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Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

Abstract:

Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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Authors: Darshna Sharma, Suban K. Sahoo

Abstract:

The detection of intracellular fluoride in human cancer cell HeLa was achieved by chemosensors derived from vitamin B6 cofactors using fluorescence imaging technique. These sensors were first synthesized by condensation of pyridoxal/pyridoxal phosphate with 2-amino(thio)phenol. The anion recognition ability was explored by experimental (UV-VIS, fluorescence and 1H NMR) and theoretical DFT [(B3LYP/6-31G(d,p)] methods in DMSO and mixed DMSO-H2O system. All the developed sensors showed both naked-eye detectable color change and remarkable fluorescence enhancement in the presence of F- and AcO-. The anion recognition was occurred through the formation of hydrogen bonded complexes between these anions and sensor, followed by the partial deprotonation of sensor. The detection limit of these sensors were down to micro(nano) molar level of F- and AcO-.

Keywords: chemosensors, fluoride, acetate, turn-on, live cells imaging, DFT

Procedia PDF Downloads 384

Authors: Jamal Al-Zain, O. El Hajjaji, T. El Bardouni

Abstract:

A (Th-U) O2 fuel pin benchmark made up of 25 w/o U and 75 w/o Th was used. In order to analyze the depletion and inventory of the fuel for the pressurized water reactor pin-cell model. The new version VIII.0 of the ENDF/B nuclear data library was used to create a data set in ACE format at various temperatures and process the data using the MAKXSF6.2 and NJOY2016 programs to process the data at the various temperatures in order to conduct this study and analyze cross-section data. The infinite multiplication factor, the concentrations and activities of the main fission products, the actinide radionuclides accumulated in the pin cell, and the total radioactivity were all estimated and compared in this study using the Monte Carlo N-Particle 6 (MCNP6.2) and DRAGON5 programs. Additionally, the behavior of the Pressurized Water Reactor (PWR) thorium pin cell that is dependent on burn-up (BU) was validated and compared with the reference data obtained using the Massachusetts Institute of Technology (MIT-MOCUP), Idaho National Engineering and Environmental Laboratory (INEEL-MOCUP), and CASMO-4 codes. The results of this study indicate that all of the codes examined have good agreements.

Keywords: PWR thorium pin cell, ENDF/B-VIII.0, MAKXSF6.2, NJOY2016, MCNP6.2, DRAGON5, fuel burn-up.

Procedia PDF Downloads 75

Authors: Zohra Salim

Abstract:

Objective: To access the relationship of primary tumor thickness with cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa. Methodology: A cross-sectional observational study was carried out on 80 Patients with biopsy-proven oral squamous cell carcinoma of buccal mucosa at Dow University of Health Sciences. All the study participants were treated with wide local excision of the primary tumor with elective neck dissection. Patients with prior head and neck malignancy or those with prior radiotherapy or chemotherapy were excluded from the study. Data was entered and analyzed on SPSS 21. Chi-squared test with 95% C.I and 80% power of the test was used to evaluate the relationship of tumor depth with cervical lymph nodes. Results: 50 participants were male, and 30 patients were female. 30 patients were in the age range of 20-40 years, 36 patients in the range of 40-60 years, while 14 patients were beyond age 60 years. Tumor size ranged from 0.3cm to 5cm with a mean of 2.03cm. Tumor depth ranged from 0.2cm to 5cm. 20% of the participants reported with tumor depth greater than 2.5cm, while 80% of patients reported with tumor depth less than 2.5cm. Out of 80 patients, 27 reported with negative lymph nodes, while 53 patients reported with positive lymph nodes. Conclusion: Our study concludes that relationship exists between the depth of primary tumor and cervical lymphadenopathy in squamous cell carcinoma of buccal mucosa.

Keywords: squamous cell carcinoma, tumor depth, cervical lymphadenopathy, buccal mucosa

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Authors: Shimaa M. Elsaeed, Reem K. Farag, Ibrahim M. Nassar

Abstract:

Hydrogel conductive polymer nanocomposite fabricated via in-situ polymerization of polyaniline (PANI) inside thermosensitive hydrogels based on hydroxy ethyl meth acrylate (HEMA) copolymer with 2-acrylamido-2-methyl propane sulfonic acid (AMPS). SEM micrographs show the nanometric size of the conductive material (polyaniline, PANI) dispersed in the hydrogel matrix. The swelling parameters of hydrogel are measured. The incorporation of PANI improves the mechanical properties and swelling up to 30,000% without breaking. X-ray diffraction shows that typical polyaniline crystallization is formed in composite, which is advantageous to increase the electrical conductivity of the composite hydrogel. Open-circuit voltage (I-V) curve fill factor of the highest photo-conversion efficiency and enhanced to use in solar cell.

Keywords: hydrogel, solar cell, conductive polymer, nanocomposite

Procedia PDF Downloads 385

Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Jake Tempo, Stephen Brough

Abstract:

Introduction and Objectives: Urine cytology has a role in the diagnosis of urothelial cancer when used alongside cystoscopy and imaging, according to the European Association of Urology guidelines. It also has a role in the surveillance post-treatment of urothelial carcinoma. Collecting and analysing urine cytology is costly and time-consuming. We investigated the use of urine cytology in an Australian regional hospital to determine whether clinicians are following international guidelines. Materials and Methods: We analysed all urine cytology requests performed in an Australian regional hospital between 1st January 2017 and 31st December 2018. We reviewed the indication for urine cytology and the patients’ case notes to determine whether urine cytology changed management. Results: During the two-year study period, 153 patients had urine cytology analysed for a variety of indications. In no cases did cytology change the outcome of patient management significantly. In total, 69 of 153 (41%) urine cytology requests were not supported by urological society guidelines. Fifty requests were for haematuria, and twenty requests were for urothelial cancer surveillance. Seven were analysed for follow-up from previous urological investigations. Nine samples were sent for ureteric obstruction of unknown origin. Conclusion: Urine cytology, even when positive, did not significantly change management for the investigation of potential urothelial cancer, and therefore, its use as a diagnostic tool for this purpose should be reconsidered. Many cytology tests are expensive, unnecessary, and not supported by urological society guidelines.

Keywords: cytology, bladder cancer, urine, urothelial carcinoma

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Authors: Narjes Ebrahimi, Soheila Alyasin, Navid Nezafat, Hossein Esmailzadeh, Younes Ghasemi, Seyed Hesamodin Nabavizadeh

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Immunotherapy with allergy vaccines is of great importance in allergen-specific immunotherapy. In recent years, B-cell epitope-based vaccines have attracted considerable attention and the prediction of epitopes is crucial to design these types of allergy vaccines. B-cell epitopes might be linear or conformational. The prerequisite for the identification of conformational epitopes is the information about allergens' tertiary structures. Bioinformatics approaches have paved the way towards the design of epitope-based allergy vaccines through the prediction of tertiary structures and epitopes. Mite allergens are one of the major allergy contributors. Several mite allergens can elicit allergic reactions; however, their structures and epitopes are not well established. So, B-cell epitopes of various groups of mite allergens (24 allergens in 6 allergen groups) were predicted in the present work. Tertiary structures of 17 allergens with unknown structure were predicted and refined with RaptorX and GalaxyRefine servers, respectively. The predicted structures were further evaluated by Rampage, ProSA-web, ERRAT and Verify 3D servers. Linear and conformational B-cell epitopes were identified with Ellipro, Bcepred, and DiscoTope 2 servers. To improve the accuracy level, consensus epitopes were selected. Fifty-four conformational and 133 linear consensus epitopes were predicted. Furthermore, overlapping epitopes in each allergen group were defined, following the sequence alignment of the allergens in each group. The predicted epitopes were also compared with the experimentally identified epitopes. The presented results provide valuable information for further studies about allergy vaccine design.

Keywords: B-cell epitope, Immunotherapy, In silico prediction, Mite allergens, Tertiary structure

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Authors: Zuzana Chaloupková, Zdeňka Marková, Václav Ranc, Radek Zbořil

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Prostate cancer is now one of the most serious oncological diseases in men with an incidence higher than that of all other solid tumors combined. Diagnosis of prostate cancer usually involves detection of related genes or detection of marker proteins, such as PSA. One of the new potential markers is PSMA (prostate specific membrane antigen). PSMA is a unique membrane bound glycoprotein, which is considerably overexpressed on prostate cancer as well as neovasculature of most of the solid tumors. Commonly applied methods for a detection of proteins include techniques based on immunochemical approaches, including ELISA and RIA. Magnetically assisted surface enhanced Raman spectroscopy (MA-SERS) can be considered as an interesting alternative to generally accepted approaches. This work describes a utilization of MA-SERS in a detection of PSMA in human blood. This analytical platform is based on magnetic nanocomposites Fe3O4@Ag, functionalized by a low-molecular selector labeled as JB303. The system allows isolating the marker from the complex sample using application of magnetic force. Detection of PSMA is than performed by SERS effect given by a presence of silver nanoparticles. This system allowed us to analyze PSMA in clinical samples with limits of detection lower than 1 ng/mL.

Keywords: diagnosis, cancer, PSMA, MA-SERS, Ag nanoparticles

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Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

Procedia PDF Downloads 152

Authors: Anne Prip, Kirsten Alling Møller, Dorte Lisbet Nielsen, Mary Jarden, Marie-Helene Olsen, Anne Kjaergaard Danielsen

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Background: The development in cancer care has shifted towards shorter hospital stays and more outpatient treatment. Today, cancer care and treatment predominantly takes place in outpatient settings where encounters between patients and health care professionals are often brief. This development will probably continue internationally as the global cancer burden seems to be growing significantly. Furthermore, the number of patients who require ambulatory treatments such as chemotherapy is increasing. Focusing on the encounters between health care professionals and patients during oncology treatment has thus become increasingly important due to a growing trend in outpatient cancer management. Objective: The aim of the systematic review was to summarize the literature from the perspective of the patient, on experiences of and the need for communication and relationships with the health care professional during chemotherapy treatment in an outpatient setting. Method: The review was designed and carried out according to the PRISMA guidelines and PICO framework. The systematic search was conducted in Medline, CINAHL, The Cochrane Library and Joanna Briggs Institute Evidence Based Practice Database. Results: In all, 1174 studies were identified by literature search. After duplicates were removed, the remaining studies (n = 1053) were screened for inclusion. Nine studies were included; qualitative (n = 5) and quantitative (n = 4) as they met the inclusions criteria. The review identified that communication and relationships between health care professionals and patients were important for the patients’ ability to cope with cancer and also had an impact on patients’ satisfaction with care in the outpatient clinic. Furthermore, the review showed that hope and positivity was a need and strategy for patients with cancer and was facilitated by health care professionals. Finally, it revealed that outpatient clinic visits framed and influenced communication and relationships. Conclusions: This review identified the significance of communication and the relationships between patients and health care professionals in the outpatient setting as it supports patients’ ability to cope with cancer. The review showed the need for health care professionals to pay attention to the relational aspects of communication in an outpatient clinic as encounters are often brief. Furthermore, the review helps to specify which elements of the communication are central in the patient-health care professional interaction from the patients' perspective. Finally, it shows a need for more research to investigate which type of interaction and intervention would be the most effective in supporting patients’ coping during chemotherapy in an outpatient clinic.

Keywords: ambulatory chemotherapy, communication, health care professional-patient relation, nurse-patient relation, outpatient care, systematic review

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Authors: Ayda Youssef, Tarek Rafaat, Iman zaky

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Purpose: Langerhans’ cell histiocytosis (LCH) is not uncommon pathology that implies aberrant proliferation of a specific dendritic (Langerhans) cell. These atypical but mature cells of monoclonal origin can infiltrate many sites of the body and may occur as localized lesions or as widespread systemic disease. Liver is one of the uncommon sites of affection. The twofold objective of this study is to illustrate the radiological presentation of this disease, and to compare these results with previously reported series. Methods and Materials: Between 2007 and 2012, 150 patients with biopsy-proven LCH were treated in our hospital, a paediatric cancer tertiary care center. A retrospective review of radiographic images and reports was performed. There were 33 patients with liver affection are stratified. All patients underwent imaging studies, mostly US and CT. A chart review was performed to obtain demographic, clinical and radiological data. They were analyzed and compared to other published series. Results: Retrospective assessment of 150 patients with LCH was performed, among them 33 patients were identified who had liver involvement. All these patients developed multisystemic disease; They were 12 females and 21 males with (n= 32), seven of them had marked hepatomegaly. Diffuse hypodense liver parenchyma was encountered in five cases, the periportal location has a certain predilection in cases of focal affection where three cases has a hypodense periportal soft tissue sheets, one of them associated with dilated biliary radicals, only one case has multiple focal lesions unrelated to portal tracts. On follow up of the patients, two cases show abnormal morphology of liver with bossy outline. Conclusion: LCH is a not infrequent disease. A high-index suspicion should be raised in the context of diagnosis of liver affection. A biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality. Liver histiocytosis are not disease specific features but should be interpreted in conjunction with the clinical history and the results of biopsy. Clinical Relevance/Application: Radiologist should be aware of different patterns of hepatobiliary histiocytosis, Thus early diagnosis and proper management of patient can be conducted.

Keywords: langerhans’ cell histiocytosis, liver, medical and health sciences, radiology

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Authors: Surekha Rathod

Abstract:

Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

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Authors: Narayan Moger, Divya B., Preethi Jambagi, Krishnaveni C. K., Apsana M. R., B. R. Patil, Basvaraj Bagewadi

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Salinity is one of the major threats to world food security. Considering the requirement for salt tolerant crop plants in the present study was undertaken to clone and transferred the salt tolerant ectA gene from marine ecosystem into agriculture crop system to impart salinity tolerance. Ectoine is the compatible solute which accumulates in the cell membrane, is known to be involved in salt tolerance activity in most of the Halophiles. The present situation is insisting to development of salt tolerant transgenic lines to combat abiotic stress. In this background, the investigation was conducted to develop transgenic tomato lines by cloning and transferring of ectA gene is an ectoine derivative capable of enzymatic action for the production of acetyl-diaminobutyric acid. The gene ectA is involved in maintaining the osmotic balance of plants. The PCR amplified ectA gene (579bp) was cloned into T/A cloning vector (pTZ57R/T). The construct pDBJ26 containing ectA gene was sequenced by using gene specific forward and reverse primers. Sequence was analyzed using BLAST algorithm to check similarity of ectA gene with other isolates. Highest homology of 99.66 per cent was found with ectA gene sequences of isolates Halomonas elongata with the available sequence information in NCBI database. The ectA gene was further sub cloned into pRI101-AN plant expression vector and transferred into E. coli DH5α for its maintenance. Further pDNM27 was mobilized into A. tumefaciens LBA4404 through tri-parental mating system. The recombinant Agrobacterium containing pDNM27 was transferred into tomato plants through In planta plant transformation method. Out of 300 seedlings, co-cultivated only twenty-seven plants were able to well establish under the greenhouse condition. Among twenty-seven transformants only twelve plants showed amplification with gene specific primers. Further work must be extended to evaluate the transformants at T1 and T2 generations for ectoine accumulation, salinity tolerance, plant growth and development and yield.

Keywords: salinity, computable solutes, ectA, transgenic, in planta transformation

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Authors: H. Y. Jung, Ju H. Park, S. M. Lee

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A sampled-data controller is presented for solid oxide fuel cell systems which is expressed by a sector bounded nonlinear model. The sector bounded nonlinear systems, which have a feedback connection with a linear dynamical system and nonlinearity satisfying certain sector type constraints. Also, the sampled-data control scheme is very useful since it is possible to handle digital controller and increasing research efforts have been devoted to sampled-data control systems with the development of modern high-speed computers. The proposed control law is obtained by solving a convex problem satisfying several linear matrix inequalities. Simulation results are given to show the effectiveness of the proposed design method.

Keywords: sampled-data control, fuel cell, linear matrix inequalities, nonlinear control

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Authors: Patcharaporn Sakulpong, Wiriya Phokhwang

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Background: Banpunrug (Love Sharing House) established in 2013 provides a community-based palliative care for patients with cancer from 7 provinces in southern Thailand. These patients come to receive outpatient chemotherapy and radiotherapy at Suratthani Cancer Hospital. They are poor and uneducated; they need an accommodation during their 30-45 day course of therapy. Methods: A community-participatory action research (PAR) was employed to establish a model of palliative care for patients with cancer. The participants included health care providers, community, and patients and families. The PAR process includes problem identification and need assessment, community and team establishment, field survey, organization founding, model of care planning, action and inquiry (PDCA), outcome evaluation, and model distribution. Results: The model of care at Banpunrug involves the concepts of HHHS model, in that Banpunrug is a Home for patients; patients live in a house comfortable like in a Hotel resource; the patients are given care and living facilities similarly to those in a Hospital; the house is a School for patients to learn how to take care themselves, how to live well with cancer, and most importantly how to prepare themselves for a good death. The house is also a humanized care school for health care providers. Banpunrug’s philosophy of care is based on friendship therapy, social and spiritual support, community partnership, patient-family centeredness, Live & Love sharing house, and holistic and humanized care. With this philosophy, the house is managed as a home of the patients and everyone involved; everything is costless for all eligible patients and their family members; all facilities and living expense are donated from benevolent people, friends, and community. Everyone, including patients and family, has a sense of belonging to the house and there is no authority between health care providers and the patients in the house. The house is situated in a temple and a community and supported by many local nonprofit organizations and healthcare facilities such as a health promotion hospital at sub-disctrict level and Suratthani Cancer Hospital. Village health volunteers and multi-professional health care volunteers have contributed not only appropriate care, but also knowledge and experience to develop a distinguishing HHHS community-based palliative care model for patients with cancer. Since its opening the house has been a home for more than 400 patients and 300 family members. It is also a model for many national and international healthcare organizations and providers, who come to visit and learn about palliative care in and by community. Conclusions: The success of this palliative care model comes from community involvement, multi-professional volunteers and distributions, and concepts of HHHS model. Banpunrug promotes a consistent care across the cancer trajectory independent of prognosis in order to strengthen a full integration of palliative

Keywords: community-based palliative care, model, participatory action research, patients with cancer

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Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

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Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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Authors: Deybith Venegas-Rojas, Jens Budde, Dominik Nörz, Manfred Jücker, Hoc Khiem Trieu

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Microfluidics is a promising approach for biomedicine cell culture experiments with microfluidic bioreactors (MBR), which can provide high precision in volume and time control over mass transport and microenvironments in small-scale studies. Nevertheless, shear stress and oxygen concentration are important factors that affect the microenvironment and then the cell culture. It is presented a novel MBR design in which differences in geometry, shear stress, and oxygen concentration were studied and optimized for cell culture. The aim is to mimic the in vivo condition with biocompatible materials and continuous perfusion of nutrients, a healthy shear stress, and oxygen concentration. The design consists of a capture system of PDMS micropillars which keep cells in place, so it is not necessary any hydrogel or complicated scaffolds for cells immobilization. Besides, the design allows continuous supply with nutrients or even any other chemical for cell experimentation. Finite element method simulations were used to study and optimize the effect of parameters such as flow rate, shear stress, oxygen concentration, micropillars shape, and dimensions. The micropillars device was fabricated with microsystem technology such as soft-lithography, deep reactive ion etching, self-assembled monolayer, replica molding, and oxygen plasma bonding. Eight different geometries were fabricated and tested, with different flow rates according to the simulations. During the experiments, it was observed the effect of micropillars size, shape, and configuration for stability and shear stress control when increasing flow rate. The device was tested with several successful HepG2 3D cell cultures. With this MBR, the aforementioned parameters can be controlled in order to keep a healthy microenvironment according to specific necessities of different cell types, with no need of hydrogels and can be used for a wide range of experiments with cells.

Keywords: cell culture, micro-bioreactor, microfluidics, micropillars, oxygen concentration, shear stress

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Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung

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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.

Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor

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Authors: Hafsa Chergui

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Malnutrition is a very common problem for hospitalized patients in general but it happens most to those who have a chronic disease such as cancer. Learned food aversions are defined as aversions which form toward foods after their ingestion has been temporally paired with illness (nausea or emesis). Learned food aversion may exert a negative impact on nutritional status and quality of life. The present review evaluates the literature derived both from laboratory animals and humans. Also, a questionnaire has been filled by patients under chemotherapy to assess the level of food aversions. This study evaluated the current research for avoiding the formation of aversions to dietary items in 200 cancer patients treated with chemotherapy. A scapegoat food or beverage can be used just before treatment to reduce the incidence of treatment-related aversions to foods in the individual s usual diet. The goal of this work is to inform the nurses and dieticians because they play a vital role in the daily assessment of the patients' nutritional status. Being aware of all the causes of malnutrition may help to suggest solutions to improve the health condition of the patient and avoid severe malnutrition.

Keywords: chemotherapy, oncology, food aversion, taste aversion

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Authors: Farzad Doostishoar, Abdolreza Hasanzadeh, Seyed Amin Ayatolahi Mousavi

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Introduction and Goals: Deuterium has different action from its isotopes hydrogen in chemical reactions and biochemical processes. It is not a significant difference in heavier atoms between the behavior of heavier isotope and the lighter One but for very lighter atoms it is significant . According to that most of the weight of all creatures body is water natural rate can be significant. In this article we want to study the effect of reduced deuterium on the fungus cell. If we saw the dependence of deuterium concentration of environment on the cells growth we can test this in invivo models too. Methods: First we measured deuterium concentration of the distillated water this analyze was operated by Arak’s heavy water company. Then the deuterium was diluted to ½ ¼ 1/8 1/16 by adding water free of deuterium for making media. In tree of samples the deuterium concentration was increased by adding D2O up to 10,50,100 times more concentrated. For candida albicans growth we used sabor medium and for aspergillus fomigatis growth we used sabor medium containing chloramphenicol. After culturing the funguses species we put the mediums for each species in the shaker incubator for 10 days in 25 centigrade. In different days and times the plates were studied morphologically and some microscopic characteristics were studied too. This experiments and cultures were repeated 3 times. Results: Statistical analyzes by paired-sample T test showed that aspergilus fomigatoos growth was decreased in concentration of 72 ppm( half deuterium concentration of negative control) significantly. In deuterium concentration reduction the growth reduce into the negative control significantly. The project results showed that candida albicans was sensitive to reduce and decrease of the deuterium in all concentrations.

Keywords: deuterium, cancer cell, growth, candida albicans

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Authors: Lakmali Anthony, Madeline Gillies

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Background: Colorectal cancer (CRC) is usually managed with surgical resection. Many of the outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO), such as Health-Related Quality of life (HRQoL), provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. HRQoL has previously been shown to be impacted by psychosocial, behavioral and disease-specific characteristics. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods: Consecutive patients who had resection of colorectal cancer in a single regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey instrument designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Demographic and disease-specific data were also collected via medical record review. Results: Forty-six patients completed the survey. Clinically significant levels of fear of recurrence as well as emotional distress, were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for CRC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL; however, the operative approach (laparoscopic vs. open) was associated with HRQoL for these patients. All psychosocial factors measured were associated with HRQoL, including cancer worry, emotional distress, body image and dispositional optimism. Conclusion: HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative colorectal cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: surgery, colorectal, cancer, PRO, HRQoL

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Authors: Asmat Nawaz, Ali Koray Erdinc, Burak Gultekin, Muhammad Tayyib, Ceylan Zafer, Kaiying Wang, M. Nadeem Akram

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In this study, a sequential deposition process is used for the fabrication of PEDOT: PSS based inverted planar perovskite solar cell. A small amount of additive deionized water (DI-H₂O) was added into PbI₂ + Dimethyl formamide (DMF) precursor solution in order to increase the solubility of PbI₂ in DMF, and finally to manipulate the surface morphology of the perovskite films. A morphology transition from needle like structure to hexagonal plates, and then needle-like again has been observed as the DI-H2O was added continuously (0.0 wt% to 3.0wt%). The latter one leads to full surface coverage of the perovskite, which is essential for high performance solar cell.

Keywords: charge carrier diffusion lengths, Methylamonium lead iodide, precursor composition, perovskite solar cell, sequential deposition

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