Search results for: inhibition of cancer cells

Authors: Ditsapelo M. McFarland

Abstract:

Background: Despite the availability of the Pap smear services in urban areas in Botswana, most women in such areas do not seem to screen regular for prevention of the cervical cancer disease. Reasons for non-use of the available Pap smear services are not well understood. Beliefs about cancer may influence participation in cancer screening in these women. The purpose of this study was to develop an instrument to measure beliefs about cervical cancer and Pap smear screening among Black women in Botswana, and evaluate the psychometric properties of the instrument. Significance: Instruments that are designed to measure beliefs about cervical cancer and screening among black women in Botswana, as well as in the surrounding region, are presently not available. Valid and reliable instruments are needed for exploration of the women’s beliefs about cervical cancer. Conceptual Framework: The Health Belief Model (HBM) provided a conceptual framework for the study. Methodology: The study was done in four phases: Phase 1: item generation: 15 items were generated from literature review and qualitative data for each of four conceptually defined HBM constructs: Perceived susceptibility, severity, benefits, and barriers (Version 1). Phase 2: content validity: Four experts who were advanced practice nurses of African descent and were familiar with the content and the HBM evaluated the content. Experts rated the items on a 4-point Likert scale ranging from: 1=not relevant, 2=somewhat relevant, 3=relevant and 4=very relevant. Fifty-five items were retained for instrument development: perceived susceptibility - 11, severity - 14, benefits - 15 and barriers - 15, all measuring on a 4-point Likert scale ranging from strongly disagree (1) to strongly agree (4). (Version 2). Phase 3: pilot testing: The instrument was pilot tested on a convenient sample of 30 women in Botswana and revised as needed. Phase 4: reliability: the revised instrument (Version 3) was submitted to a larger sample of women in Botswana (n=300) for reliability testing. The sample included women who were Batswana by birth and decent, were aged 30 years and above and could complete an English questionnaire. Data were collected with the assistance of trained research assistants. Major findings: confirmatory factor analysis of the 55 items found that a number of items did not adequately load in a four-factor solution. Items that exhibited reasonable reliability and had low frequency of missing values (n=36) were retained: perceived barriers (14 items), perceived benefits (8 items), perceived severity (4 items), and perceived susceptibility (10 items). confirmatory factor analysis (principle components) for a four factor solution using varimax rotation demonstrated that these four factors explained 43% of the variation in these 36 items. Conclusion: reliability analysis using Cronbach’s Alpha gave generally satisfactory results with values from 0.53 to 0.89.

Keywords: cervical cancer, factor analysis, psychometric evaluation, varimax rotation

Procedia PDF Downloads 127

Authors: Jaci Marie Mastrandrea, Rosario Haro

Abstract:

Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening and intervention is directly associated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project was to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated, evidence-based PC referral criteria. The tool was initially implemented using paper forms, and data was collected over a period of eight weeks. Patients were screened by nurses on the SLCTC oncology treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher received an educational handout on the topic of PC and education about PC and symptom management. A score of five or higher indicates that PC referral is strongly recommended, and the patient’s EHR is flagged for the oncology provider to review orders for PC referral. The PSNA tool was approved by Sky Lakes administration for full integration into Epic-Beacon. The project lead collaborated with the Sky Lakes’ information systems team and representatives from Epic on the tool’s aesthetic and functionality within the Epic system. SLCTC nurses and physicians were educated on how to document the PSNA within Epic and where to view results. Results: Prior to the implementation of the PSNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the completed screening assessments of 100 patients under active treatment at the SLCTC. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting criteria were flagged in EPIC for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met the criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative and supportive care, symptom management, outpatient oncology, palliative screening tool

Procedia PDF Downloads 112

Authors: Samah Lakehal, A. Meliani, F. Z. Benrebiha, C. Chaouia

Abstract:

In the last few years, due to the misuse of antibiotics and an increasing incidence of immunodeficiency-related diseases, the development of microbial drug resistance has become more and more of a pressing problem. Recently, natural products from medicinal plants represent a fertile ground for the development of novel antibacterial agents. Plants essential oils have come more into the focus of phytomedicine. The present study describes antimicrobial activity of Rosmarinus officinalis L. essential oil known medicinally for its powerful antibacterial properties. The essential oil of rosemary obtained by hydrodistillation (using Clevenger type apparatus) growing in Algeria (Djelfa city of south Algeria) was investigated by GC-MS. The essential oil yield of the study was 1.4 %. The major components were found to be camphor, camphene, 1,8-cineole. The essential oil has been tested for antimicrobial activity against eight bacteria (Gram-negative and Gram-positive), and three fungi including Candida albicans. Inhibition of growth was tested by the agar diffusion method based on the determination of the diameter of inhibition. The oil was found to have significant antibacterial activity and therefore can be used as a natural antimicrobial agent for the treatment of several infectious diseases caused by those germs, which have developed resistance to antibiotics.

Keywords: antimicrobial activity, Rosmarinus officinalis L., essential oils, GC/MS, camphor

Procedia PDF Downloads 392

Authors: Roman Major, Klaudia Trembecka- Wojciga, Juergen Markus Lackner, Boguslaw Major

Abstract:

The future and the development of science is therefore seen in interdisciplinary areas such as bio medical engineering. Self-assembled structures, similar to stem cell niches would inhibit fast division process and subsequently capture the stem cells from the blood flow. By means of surface topography and the stiffness as well as micro structure progenitor cells should be differentiated towards the formation of endothelial cells monolayer which effectively will inhibit activation of the coagulation cascade. The idea of the material surface development met the interest of the clinical institutions, which support the development of science in this area and are waiting for scientific solutions that could contribute to the development of heart assist systems. This would improve the efficiency of the treatment of patients with myocardial failure, supported with artificial heart assist systems. Innovative materials would enable the redesign, in the post project activity, construction of ventricular heart assist.

Keywords: bio-inspired materials, electron microscopy, haemocompatibility, niche-like structures, thin coatings

Procedia PDF Downloads 478

Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

Abstract:

With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

Procedia PDF Downloads 472

Authors: Asaf Toker

Abstract:

Matricelf developed a technology that enables the production of autologous engineered tissue composed of matrix and cells derived from patients Omentum biopsy. The platform showed remarkable pre-clinical results for several medical conditions. The company recently licensed the technology that enabled scientist at Tel Aviv university that 3D printed a human heart from human cells and matrix for the first time in human history. The company plans to conduct its first human clinical trial for Acute Spinal Cord Injury (SCI) early in 2023.

Keywords: tissue engineering, regenerative medicine, spinal Cord Injury, autologous implants, iPSC

Procedia PDF Downloads 126

Authors: Hulya Tuba Kiyan, Nilgun Ozturk

Abstract:

Gentiana, a member of Gentianaceae, is represented by approximately 400 species in the world and 12 species in Turkey. Flavonoids, iridoids, triterpenoids and also xanthones are the major compounds of this genus, have been previously reported to have antiinflammatory, antimicrobial, antioxidant, hepatoprotective, hypotensive, hypoglycaemic, DNA repair and immunomodulatory properties. The methanolic extract of the aerial parts of Gentiana brachyphylla Vill. from Turkey was evaluated for its biological activities and its total phenolic content in the present study. According to the antioxidant activity results, G. brachyphylla methanolic extract showed very strong anti-DNA damage antioxidant activity with an inhibition of 81.82%. It showed weak ferric-reducing power with a EC50 value of 0.65 when compared to BHT (EC50 = 0.2). Also, at 0.5 mg/ml concentration, the methanolic extract inhibited ABTS radical cation activity with an inhibition of 20.13% when compared to Trolox (79.01%). Chelating ability of G. brachyphylla was 44.71% whereas EDTA showed 78.87% chelating activity at 0.2 mg/ml. Also G. brachyphylla showed weak 27.21% AChE, 20.23% BChE, strong 67.86% MAO-A and moderate 50.06% MAO-B, weak 19.14% COX-1, 29.11% COX-2 inhibitory activities at 0.25 mg/ml. The total phenolic content of G. brachyphylla was 156.23 ± 2.73 mg gallic acid equivalent/100 g extract.

Keywords: antioxidant activity, cholinesterase inhibitory activity, Gentiana brachyphylla Vill., total phenolic content

Procedia PDF Downloads 201

Authors: Hammad Khan, Wookeun Bae

Abstract:

The objective of this study was to achieve, optimize and control the highly loaded and efficient nitrite production having suitability for autotrophic and heterotrophic denitritation. A lab scale CSTR for partial and full nitritation was operated to treat the livestock manure digester liquor having an ammonium concentration of ~2000 mg-NH4+-N/L and biodegradable contents of ~0.8 g-COD/L. The experiments were performed at 30°C, pH: 8.0, DO: 1.5 mg/L and SRT ranging from 7-20 days. After 125 days operation, >95% nitrite buildup having the ammonium loading rate of ~3.2 kg-NH4+-N/m3-day was seen with almost complete ammonium conversion. On increasing the loading rate further (i-e, from 3.2-6.2 kg-NH4+-N/m3-day), stability of the system remained unaffected. On decreasing the pH from 8 to 7.5 and further 7.2, removal rate can be easily controlled as 95%, 75% and even 50%. Results demonstrated that nitritation stability and desired removal rates are controlled by a balance of simultaneous inhibition by FA & FNA, pH affect and DO limitation. These parameters proved to be effective even to produce an appropriate influent for anammox. In addition, a mathematical model, identified through the occurring biological reactions, is proposed to optimize the full and partial nitritation process. The proposed model present relationship between pH, ammonium and produced nitrite for full and partial nitritation under the varying concentrations of DO, and simultaneous inhibition by FA and FNA.

Keywords: stable nitritation, high loading, autrophic denitritation, hetrotrophic denitritation

Procedia PDF Downloads 274

Authors: Mohammad Jamil Abd AlGhani

Abstract:

The natural native antioxidants N,N-P-methyl phenyl acetone and N,N-phenyl acetone were isolated from the Iraqi crude oil region of Kirkuk by ion exchange and their structure was characterized by spectral and chemical analysis methods. Tetraline was used as a liquid hydrocarbon to detect the efficiency of isolated molecules at elevated temperature (393 K) that it has physicochemical specifications and structure closed to hydrocarbons fractionated from crude oil. The synthesized universal antioxidant 2,6-ditertiaryisobutyl-p-methyl phenol (Unol) with known stochiometric coefficient of inhibition equal to (2) was used as a model for comparative evaluation at the same conditions. Modified chemiluminescence method was used to find the amount of absorbed oxygen and the induction periods in and without the existence of isolated antioxidants molecules. The results of induction periods and quantity of absorbed oxygen during the oxidation process were measured by manometric installation. It was seen that at specific equal concentrations of N,N-phenyl acetone and N, N-P-methyl phenyl acetone in comparison with Unol at 393 K were with (2) and (2.5) times efficient than do Unol. It means that they had the ability to inhibit the formation of new free radicals and prevent the chain reaction to pass from the propagation to the termination step rather than decomposition of formed hydroperoxides.

Keywords: antioxidants, chemiluminescence, inhibition, Unol

Procedia PDF Downloads 200

Authors: Eva Slaninova, Diana Cernayova, Zuzana Sedrlova, Katerina Mrazova, Petr Sedlacek, Jana Nebesarova, Stanislav Obruca

Abstract:

Cyanobacteria are gram-negative prokaryotes belonging to a group of photosynthetic bacteria. In comparison with heterotrophic microorganisms, cyanobacteria utilize atmospheric nitrogen and carbon dioxide without any additional substrates. This ability of these microorganisms could be employed in biotechnology for the production of bioplastics, concretely polyhydroxyalkanoates (PHAs) which are primarily accumulated as a storage material in cells in the form of intracellular granules. In this study, there two cyanobacterial cultures from genera Synechocystis were used, namely Synechocystic sp. PCC 6803 and Synechocystis salina CCALA 192. There were optimized and used several various approaches, including microscopic techniques such as cryo-scanning electron microscopy (Cryo-SEM) and transmission electron microscopy (TEM), and fluorescence lifetime imaging microscopy using Nile red as a fluorescent probe (FLIM). Due to these instrumental techniques, the morphology of intracellular space and surface of cells were characterized. The next group of methods which were employed was spectroscopic techniques such as UV-Vis spectroscopy measured in two modes (turbidimetry and integration sphere) and Fourier transform infrared spectroscopy (FTIR). All these diverse techniques were used for the detection and characterization of pigments (chlorophylls, carotenoids, phycocyanin, etc.) and PHAs, in our case poly (3-hydroxybutyrate) (P3HB). To verify results, gas chromatography (GC) was employed concretely for the determination of the amount of P3HB in biomass. Cyanobacteria were also characterized as polyhydroxybutyrate producers by flow cytometer, which could count cells and at the same time distinguish cells including P3HB and without due to fluorescent probe called BODIPY and live/dead fluorescent probe SYTO Blue. Based on results, P3HB content in cyanobacteria cells was determined, as also the overall fitness of the cells. Acknowledgment: Funding: This study was partly funded by the projectGA19-29651L of the Czech Science Foundation (GACR) and partly funded by the Austrian Science Fund (FWF), project I 4082-B25.

Keywords: cyanobacteria, fluorescent probe, microscopic techniques, poly(3hydroxybutyrate), spectroscopy, chromatography

Procedia PDF Downloads 229

Authors: K. Shaloom Mbambu, M. Pascal Tshimbalanga, K. Ruth Mutala, K. Roger Kabuya, N. Dieudonné Kabeya, Y. L. Kabeya Mukeba

Abstract:

In this article, the authors examine the even more worrying situation of girls in sub-Saharan Africa. Two-girls on five are private of Global Education, which represents a real loss to the development of communities and countries. Cultural traditions, poverty, violence, early and forced marriages, early pregnancies, and many other gender inequalities were the causes of this cancer development. Namely, "it is no more efficient development tool that is educating girls." The non-schooling of girls and their lack of supervision by liberal professions have serious consequences for the life of each of them. To improve the conditions of their inferior status, girls to men introduce poverty and health risks. Raising awareness among parents and communities on the importance of girls' education, improving children's access to school, girl-boy equality with their rights, creating income, and generating activities for girls, girls, and girls learning of liberal trades to make them self-sufficient. Organizations such as the United Nations Organization can save the children. ASEAD and the AEDA group are predicting the impact of this cancer on the development of a nation's future generation must be preserved.

Keywords: young girl, Sub-Saharan Africa, higher and vocational education, development, society, environment

Procedia PDF Downloads 255

Authors: Dinara Ikramova, Karin A. Hing, Simon C. F. Rawlinson

Abstract:

Silicate-substituted hydroxyapatite (SiHA) has been shown to enhance bone regeneration in vivo compared with phase pure stoichiometric hydroxyapatite. Evidence suggests that substrate chemistry dependent formation of a permissive protein layer on the surface of synthetic bone graft substitute materials is key for bioactivity and cell attachment. However, little information is available on whether the substrate chemistry may affect cell migration and recruitment. The aim of this study is to investigate whether or not human Mesenchymal Stem Cells (hMSCs) exhibit a chemotactic response to SiHA porous granules and if it can be linked to either the ion exchange or protein sequestering and enrichment on the surface of the material. 150mg of SiHA granules with 80% total porosity and 20% strut porosity were incubated in 1ml of either Serum Free Media (SFM) or 10% Serum Containing Media (SCM) under static cell culture conditions (37°C, 5% CO2) in absence of cells. Protein sequestering and exchange of calcium, phosphate and silicate ions were analysed at 0.5, 1, 2, 4, 8, 16 and 24 hours with n=12 per time point. Migration of hMSCs in the presence of 150mg of SiHA granules was assessed over 24 hours using a modified transwell migration system in either SFM or SCM (n=6) with 30% serum containing media acting as a positive control. At 24 hours protein sequestering and ionic exchange were analysed, and the number of cells was quantified using a high throughput confocal microscope (IN Cell Analyser 6000). In acellular condition, both calcium and phosphate ion concentrations in media showed a decrease at 24 hours which was greater in SFM than in SCM. This suggests possible formation and precipitation of a bone like apatite on the surface of SiHA. Reduction in this activity observed in SCM indicates that the presence of serum proteins is interfering with the ion exchange at the material and media interface. Adsorbed protein levels showed fluctuation over time followed by sharp decrease at 24 hours, suggesting a possible protein rearrangement on the surface of the material. The ion analysis performed on SFM and SCM after 24-hour incubation with cells in the presence of granules showed a greater reduction in phosphate concentration in both SFM and SCM compared to phosphate levels in acellular condition. Silicate concentration in SCM increased from 1.6mM (absence of cells) to 5.1mM (presence of cells). This indicates that the cells are promoting the uptake of phosphate and release of silicate ions. No significant change was seen in levels of adsorbed proteins in the presence and absence of cells. Further analysis is required to determine whether the species of these proteins change over time. The analysis of cell migration after 24-hour incubation showed more cells migrating towards the granules, 12.7% in SFM and 8.3% in SCM, than in positive control, 4.5% in SFM and 3.6% in SCM respectively. These results suggest that SiHA has a chemotactic activity independent of serum proteins. A property which has not previously been demonstrated for a synthetic bone graft material.

Keywords: cell migration, hMSCs, SiHA, transwell migration system

Procedia PDF Downloads 131

Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren

Abstract:

We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.

Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values

Procedia PDF Downloads 154

Authors: Charles Lee

Abstract:

The Principal Orthogonal Decomposition (POD) technique has been used as a model reduction tool for many applications in engineering and science. In principle, one begins with an ensemble of data, called snapshots, collected from an experiment or laboratory results. The beauty of the POD technique is that when applied, the entire data set can be represented by the smallest number of orthogonal basis elements. It is the such capability that allows us to reduce the complexity and dimensions of many physical applications. Mathematical formulations and numerical schemes for the POD method will be discussed along with applications in NASA’s Deep Space Large Antenna Arrays, Satellite Image Reconstruction, Cancer Detection with DNA Microarray Data, Maximizing Stock Return, and Medical Imaging.

Keywords: reduced-order methods, principal component analysis, cancer detection, image reconstruction, stock portfolios

Procedia PDF Downloads 84

Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

Abstract:

Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

Procedia PDF Downloads 158

Authors: V. K. Srivastava

Abstract:

The chemistry of compounds containing transition metals bound to sulfur containing ligands has been actively studied. Interest in these compounds arises from the identification of the biological importance of iron-sulfur containing proteins as well as the unusual behaviour of several types of synthetic metal-sulfur complexes. Metal complexes (C₆H₅)₄P)₂ Pt(Mos₄)₂, (C₆H₅)₄P)₂ Pd(MoS₄)₂, (C₆H₅)₄P)₂ Ni(MoS₄)₂ of bioinorganic relevance were investigated. The complexes [M(M'S₄)₂]²⁻ were prepared with high yield and purity as salts of the variety of organic cations. The diamagnetism and spectroscopic properties of these complexes confirmed that their structures are essentially equivalent with two bidentate M'S₄²⁻ ligands coordinated to the central d⁸ metal in a square planer geometry. The interaction of the complexes with CT-DNA was studied. Results showed that metal complexes increased DNA's relative viscosity and quench the fluorescence intensity of EB bound to DNA. In antimicrobial activities, all complexes showed good antimicrobial activity higher than ligand against gram positive, gram negative bacteria and fungi. The antitumor properties have been tested in vitro against two tumor human cell lines, Hela (derived from cervical cancer) and MCF-7 (derived from breast cancer) using metabolic activity tests. Result showed that the complexes are promising chemotherapeutic alternatives in the search of anticancer agents.

Keywords: anti cancer, biocidal, DNA binding, spectra

Procedia PDF Downloads 159

Authors: Inayat Ur Rahman Arshad

Abstract:

Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non caloric sweet Steviol Glycosides (SGs). The purpose of the study is to optimize sugar concentration, pH level and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes were inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Maximum callus induction 100, 87.5 and 85.33% was resulted in the medium supplemented with 30g/l sucrose, pH maintained at 5.5 and inoculated with 1.25g inoculum respectively. Similarly, the highest fresh weight 65.00, 75.50 and 50.53g/l were noted in medium fortified with 40g/l sucrose, inoculated 1.25g inoculum and 6.0 pH level respectively. However, the callus developed in medium containing 50g/l sucrose found highly antibacterial potent with 27.3 and 26.5mm inhibition zone against P. vulgaris and B. subtilize respectively. Similarly, the callus grown on medium inoculated with 1.00g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72mm inhibition zones respectively. However, in the case of pH levels the medium maintained at 6.5pH showed maximum antibacterial activity against P. vulgaris, B.subtilis and E.coli with 27.9, 25 and 23.72mm respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment the standard antibacterial agent Streptomycin showed the highest inhibition zones from the rest of the callus extract, however the pure DMSO (Dimethyl Sulfoxide) caused no inhibitory zone against any bacteria. From these findings it is concluded that among various levels sucrose at the rate of 40g L-1, pH 6.0 and inoculums 0.75g was found best for most of the growth and quality attributes including fresh weight, dry weight and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana

Keywords: Steviol Glycosides, Skoog, Murashige, Clavebactor michiganensis

Procedia PDF Downloads 87

Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

Abstract:

Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

Procedia PDF Downloads 351

Authors: Inayat Ur Rahman Arshad

Abstract:

Background: Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non-caloric sweet steviol glycosides (SGs). Purpose: The purpose of the study is to optimize sugar concentration, pH level, and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Method: Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes was inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Results: Maximum callus induction 100, 87.5, and 85.33% resulted in the medium supplemented with 30 g/l sucrose, pH maintained at 5.5, and inoculated with 1.25g inoculum, respectively. Similarly, the highest fresh weights 65.00, 75.50, and 50.53 g/l were noted in a medium fortified with 40 g/l sucrose, inoculated 1.25g inoculum, and 6.0 pH level, respectively. However, the callus developed in a medium containing 50 g/l sucrose was found to be highly antibacterial potent with 27.3 and 26.5 mm inhibition zone against P. vulgaris and B. subtilis, respectively. Similarly, the callus grown on a medium inoculated with 1.00 g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72 mm inhibition zone, respectively. However, in the case of pH levels, the medium maintained at 6.5 pH showed maximum antibacterial activity against P. vulgaris, B.subtilis, and E.coli with 27.9, 25, and 23.72 mm, respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment, the standard antibacterial agent Streptomycin showed the highest inhibition zones among the rest of the callus extract; however, the pure dimethyl sulfoxide (DMSO) caused no inhibitory zone against any bacteria. Conclusion: From these findings, it is concluded that among various levels, sucrose @ 40 g L⁻¹, pH 6.0, and inoculums at 0.75 g were found best for most of the growth and quality attributes, including fresh weight, dry weight, and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana.

Keywords: Stevia rebaudiana, Steviol Glycosides, callus, Xanthomonas campestris

Procedia PDF Downloads 82

Authors: Leo Nnamdi Ozurumba-Dwight

Abstract:

Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

Procedia PDF Downloads 176

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

Abstract:

Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

Procedia PDF Downloads 80

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

Abstract:

Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

Procedia PDF Downloads 320

Authors: Ekaterina Zvorykina

Abstract:

Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

Procedia PDF Downloads 156

Authors: A. Hamieh, Z. Olama, H. Holail

Abstract:

Drinking Water Distribution Systems provide opportunities for microorganisms that enter the drinking water to develop into biofilms. Antimicrobial agents, mainly chlorine, are used to disinfect drinking water, however, there are not yet standardized disinfection strategies with reliable efficacy and development of novel anti-biofilm strategies is still of major concern. In the present study the ability of Lactobacillus acidophilus and Streptomyces sp. cell free supernatants to inhibit the bacterial biofilm formation in Drinking Water Distribution System in Lebanon was investigated. Treatment with cell free supernatants of Lactobacillus acidophilus and Streptomyces sp. at 20% concentration resulted in average biofilm inhibition (52.89 and 39.66% respectively). A preliminary investigation about the mode of action of biofilm inhibition revealed that cell free supernatants showed no bacteriostatic or bactericidal activity against all the tested isolates. Pre-coating wells with supernatants revealed that Lactobacillus acidophilus cell free supernatant inhibited average biofilm formation (62.53%) by altering the adhesion of bacterial isolates to the surface, preventing the initial attachment step, which is important for biofilm production.

Keywords: biofilm, cell free supernatant, distribution system, drinking water, lactobacillus acidophilus, streptomyces sp, adhesion

Procedia PDF Downloads 435

Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

Abstract:

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

Procedia PDF Downloads 346

Authors: H. Mazouz, A. Belghachi, F. Hadjaj

Abstract:

Solar cells used in orbit are exposed to radiation environment mainly protons and high energy electrons. These particles degrade the output parameters of the solar cell. The aim of this work is to characterize the effects of electron irradiation fluence on the J (V) characteristic and output parameters of gaAs solar cell by numerical simulation. The results obtained demonstrate that the electron irradiation-induced degradation of performances of the cells concerns mainly the short circuit current.

Keywords: gaAs solar cell, MeV electron irradiation, irradiation fluence, short circuit

Procedia PDF Downloads 474

Authors: Saeed Moarrefi, Shou-Han Zhou, Liyuan Fan

Abstract:

Coupling with solid oxide fuel cells, methane dry reforming is a promising pathway for energy production while mitigating carbon emissions. However, the influence of carbon dioxide and electrochemical reactions on the internal dry reforming reaction within the fuel cells remains debatable, requiring accurate kinetic models to describe the internal reforming behaviors. We employed the Power-Law and Langmuir Hinshelwood–Hougen Watson models in an electrolyte-supported solid oxide fuel cell with a NiO-GDC-YSZ anode. The current density used in this study ranges from 0 to 1000 A/m2 at 973 K to 1173 K to estimate various kinetic parameters. The influence of the electrochemical reactions on the adsorption terms, the equilibrium of the reactions, the activation energy, the pre-exponential factor of the rate constant, and the adsorption equilibrium constant were studied. This study provides essential parameters for future simulations and highlights the need for a more detailed examination of reforming kinetic models.

Keywords: dry reforming kinetics, Langmuir Hinshelwood–Hougen Watson, power-law, SOFC

Procedia PDF Downloads 23

Authors: Priya Patel, Paresh Patel, Mihir Raval

Abstract:

Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

Procedia PDF Downloads 429

Authors: Azhar Jabareen, Mahmoud Huleihel

Abstract:

BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

Procedia PDF Downloads 248

Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

Abstract:

Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

Procedia PDF Downloads 330