Search results for: cancer subtypes
814 Comparison of Stereotactic Body Radiation Therapy Virtual Treatment Plans Obtained With Different Collimators in the Cyberknife System in Partial Breast Irradiation: A Retrospective Study
Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş
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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.
Procedia PDF Downloads 111813 Working Memory and Audio-Motor Synchronization in Children with Different Degrees of Central Nervous System's Lesions
Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin
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Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory
Procedia PDF Downloads 290812 A Gold-Based Nanoformulation for Delivery of the CRISPR/Cas9 Ribonucleoprotein for Genome Editing
Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa
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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology
Procedia PDF Downloads 91811 Smoking and Alcohol Consumption Predicts Multiple Head and Neck Cancers
Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern
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Introduction: It is well known that patients with Head and Neck Cancer (HNC) are at increased risk of subsequent head and neck cancers due to various aetiologies. Aim: We sought to determine the factors contributing to an increased risk of subsequent HNC primaries, and also to evaluate whether Aboriginal patients are at increased risk. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. We collected patient data including smoking and alcohol consumption, tumour and treatment data, and data on subsequent HNC primaries. Results: A subsequent HNC primary was seen in 37 patients (11.6%) overall. There was no significant difference in the rate of second primary HNCs between Aboriginal patients (12.5%) and nonAboriginal patients (11.2%) (p=0.408). Subsequent HNCs, were strongly associated with smoking and alcohol consumption however, with 95% of patients with a second primary being ever-smokers, and 54% of patients with a second primary having a history of excessive alcohol consumption. In the 37 patients with multiple HNC primaries, there were a total of 57 HNCs, with 29 patients having two primaries, six patients having 3 HNC primaries, one patient with four, and one with six. 54 out of the 57 cancers were in ever smokers (94.7%). There were only two multiple HNC primaries in a never smoker, non-drinker, and these cases were of unknown etiology with HPV/p16 status unknown in both cases. In the whole study population, there were 32 HPV-positive HNCs, and 67 p16-positive HNCs, with only two 2 nd HNCs in a p16-positive case, giving a rate of 3% in the p16+ population, which is actually much lower than the rate of second primaries seen in the overall population (11.6%), and was highest in the p16-negative population (15.7%). This suggests that p16-positivity is not a strong risk factor for subsequent primaries, and in fact p16-negativity appeared to be associated with increased risk, however this data is limited by the large number of patients without documented p16 status (45.3% overall, 12% for oropharyngeal, and 59.6% for oral cavity primaries had unknown p16 status). Summary: Subsequent HNC primaries were strongly associated with smoking and alcohol excess. Second and later HNC primaries did not appear to occur at increased rates in Aboriginal patients compared with non-Aboriginal patients, and p16-positivity did not predict increased risk, however p16-negativity was associated with an increased risk of subsequent HNCs.Keywords: head and neck cancer, multiple primaries, aboriginal, p16 status, smoking, alcohol
Procedia PDF Downloads 61810 Preparation Nanocapsules of Chitosan Modified With Selenium Extracted From the Lactobacillus Acidophilus and Their Anticancer Properties
Authors: Akbar Esmaeili, Mahnoosh Aliahmadi
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This study synthesized a modified imaging of gallium@deferoxamine/folic acid/chitosan/polyaniline/polyvinyl alcohol (Ga@DFA/FA/CS/PANI/PVA). It contains Morus nigra extract by selenium nanoparticles prepared from Lactobacillus acidophilus. Using the impregnation method, Se nanoparticles were then deposited on (Ga@DFA/FA/ CS/PANI/PVA). The modified contrast agents were mixed with M. nigra extract, and investigated their antibacterial activities by applying to L929 cell lines. The influence of variable factors, including 1. surfactant, 2. solvent, 3. aqueous phase, 4. pH, 5. buffer, 6. minimum Inhibitory concentration (MIC), 7. minimum bactericidal concentration (MBC), 8. cytotoxicity on cancer cells., 9. antibiotic, 10. antibiogram, 11. release and loading, 12. the emotional effect, 13. the concentration of nanoparticles, 14. olive oil, and 15. they have investigated thermotical methods. The structure and morphology of the synthesized contrast agents were characterized by zeta potential sizer analysis (ZPS), X-Ray diffraction (XRD), Fourier-transform infrared (FT-IR), energy dispersive X-ray (EDX), ultraviolet–visible (UV–Vis) spectra, and scanning electron microscope (SEM). The experimental section was conducted and monitored by response surface methods (RSM), MTT, MIC, MBC, and cancer cytotoxic conversion assay. Antibiogram testing of NCs on Pseudomonas aeruginosa bacteria was successful and obtained MIC = 2 factors with less harmful effect. All experimental sections confirmed that our synthesized particles have potent antioxidant properties. Antibiogram testing revealed that NPS could kill P. aeruginosa and P. aeruginosa. A variety of synthetic conditions were done by diffusion emulsion method by varying parameters, the optimum state of DFA release Ga@DFA/FA/CS/PANI/PVA NPs (6 ml) with pH = 5.5, time = 3 h, NCs and DFA (3 mg), and achieved buffer (20 ml). DFA in Ga@DFA/FA/ CS/PANI/PVA was released and showed an absorption peak at 378 nm by applying a 300-rpm magnetic rate. In this report, Ga decreased the harmful effect on the human body.Keywords: nanocapsules, technolgy, biology, nano
Procedia PDF Downloads 30809 Identification and Quantification of Sesquiterpene Lactones of Sagebrush (Artemisia tridentate) and Its Chemical Modification
Authors: Rosemary Anibogwu, Kavita Sharma, Karl De Jesus
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Sagebrush is an abundant and naturally occurring plant in the Intermountain West region of the United States. The plant contains an array of bioactive compounds such as flavonoids, terpenoids, sterols, and phenolic acids. It is important to identify and characterize these compounds because Native Americans use sagebrush as herbal medicine. These compounds are also utilized for preventing infection in wounds, treating headaches and colds, and possess antitumor properties. This research is an exploratory study on the sesquiterpene present in the leaves of sagebrush. The leaf foliage was extracted with 100 % chloroform and 100 % methanol. The percentage yield for the crude was considerably higher in chloroform. The Thin Layer Chromatography (TLC) analysis of the crude extracted unveiled a brown band at Rf = 0.25 and a dark brown band at Rf = 0.74, along with three unknown faint bands the 254 nm UV lamp. Furthermore, the two distinct brown (Achillin) and dark brown band (Hydroxyachillin) in TLC were further utilized in the isolation of pure compounds with column chromatography. The structures of Achillin and Hydroxyachillin were elucidated based on extensive spectroscopic analysis, including TLC, High-Performance Liquid Chromatography (HPLC), 1D- and 2D-Nuclear Magnetic Resonance (NMR), and Mass Spectroscopy (MS). The antioxidant activities of crude extract and three pure compounds were evaluated in terms of their peroxyl radical scavenging by Ferric Reducing Ability of Plasma (FRAP) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude extract showed the antioxidant activity of 18.99 ± 0.51 µmol TEg -1 FW for FRAP and 11.59 ± 0.38 µmol TEg -1 FW for DPPH. The activities of Achillin, Hydroxyachillin, and Quercetagetin trimethyl ether were 13.03, 15.90 and 14.02 µmol TEg -1 FW respectively for the FRAP assay. The three purified compounds have been submitted to the National Cancer Institute 60 cancer cell line for further study.Keywords: HPLC, nuclear magnetic resonance spectroscopy, sagebrush, sesquiterpene lactones
Procedia PDF Downloads 121808 New Roles of Telomerase and Telomere-Associated Proteins in the Regulation of Telomere Length
Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng
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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.Keywords: aging, hTERT, telomerase, telomeres, human cells
Procedia PDF Downloads 418807 Synthesis of Highly Stable Multi-Functional Iron Oxide Nanoparticles for Active Mitochondrial Targeting in Immunotherapy
Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour
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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle
Procedia PDF Downloads 68806 Exposure to Ionizing Radiation Resulting from the Chernobyl Fallout and Childhood Cardiac Arrhythmia: A Population Based Study
Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain
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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children
Procedia PDF Downloads 238805 Outcome of Unilateral Retinoblastoma: A Ten Years Experience of Children's Cancer, Hospital Egypt
Authors: Ahmed Elhussein, Hossam El-Zomor, Adel Alieldin, Mahmoud A. Afifi, Abdullah Elhusseiny, Hala Taha, Amal Refaat, Soha Ahmed, Mohamed S. Zagloul
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Background: A majority of children with retinoblastoma (60%) have a disease in one eye only (unilateral disease). This is a retrospective study to evaluate two different treatment modalities in those patients for saving their lives and vision. Methods: Four hundred and four patients were diagnosed with unilateral intraocular retinoblastoma at Children’s Cancer, Hospital Egypt (CCHE) through the period of July/2007 until December/2017. Management strategies included primary enucleation versus ocular salvage treatment. Results: Patients presented with mean age 24.5 months with range (1.2-154.3 months). According to the international retinoblastoma classification, Group D (n=172, 42%) was the most common, followed by group E (n=142, 35%), group C (n=63, 16%), and group B (n=27, 7%). All patients were alive at the end of the study except four patients who died, with 5-years overall survival 98.3% [CI, (96.5-100%)]. Patients presented with advanced disease and poor visual prognosis (n=241, 59.6%) underwent primary enucleation with 6 cycles adjuvant chemotherapy if they had high-risk features in the enucleated eye; only four patients out of 241 ended-up either with extraocular metastasis (n=3) or death (n=1). While systemic chemotherapy and focal therapy were the primary treatment for those who presented with favorable disease status and good visual prognosis (n=163, 40.4%); seventy-seven patients of them (47%) ended up with a pre-defined event (enucleation, EBRT, off protocol chemotherapy or 2ry malignancy). Ocular survival for patients received primary chemotherapy + focal therapy was [50.9% (CI, 43.5-59.6%)] at 3 years and [46.9% (CI,39.3-56%)] at 5 years. Comparison between upfront enucleation and primary chemotherapy for occurrence of extraocular metastasis revealed that there was no statistical difference between them except in group D (p value). While for occurrence of death, no statistical difference in all classification groups. Conclusion: In retinoblastoma, primary chemotherapy is a reasonable option and has a good probability for ocular salvage without increasing the risk of metastasis in comparison to upfront enucleation except in group D.Keywords: CCHE, chemotherapy, enucleation, retinoblastoma
Procedia PDF Downloads 147804 Derivation of Human NK Cells from T Cell-Derived Induced Pluripotent Stem Cells Using Xenogeneic Serum-Free and Feeder Cell-Free Culture System
Authors: Aliya Sekenova, Vyacheslav Ogay
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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system
Procedia PDF Downloads 319803 Impact of Hormone Replacement Therapy on Body Composition Analysis of Women during Perimenopause: A Framework for Action
Authors: Varsha Chorsiya, Pooja Aneja, Dhananjay Kaushik, Abhinav Yadav
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Intoduction: Women’s Health Initiatives (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of obesity, heart disease, breast cancer and colorectal cancer, and fractures in menopause women. The utility of the present research work determines to find the role of Hormone Replacement Therapy (HRT) in changing the different component of body composition during perimenopause period. Methods: A comparative cross-sectional study included 30 subjects, aged between 40 and 50 years which were assigned into 2 groups i.e. 15 subjects in HRT (Group A) and 15 subjects in non-HRT (Group B). The subjects were taken from the hospitals and clinics of Faridabad undergoing HRT in supervision of the consultant gynecologist. The informed consents were signed before including the participants in the study. The body composition and lipid profile were evaluated for all the subjects. Result and Discussion: The BMI, body density, percent body fats and fat mass in both groups showed statistically significant differences i.e. p < 0.05. Our study did not reveal any statistically significant difference between non-HRT and HRT for lipid profile composition of HDL, LDL, VLDL, ratio, triglycerides and total cholesterol although these indicators (LDL, VLDL, ratio, triglycerides and total cholesterol) showed difference clinically with a higher mean values for non-HRT as compared to HRT group. The mean value for HDL was higher for HRT group in contrast to non-HRT group. The result clearly showed that HRT group has a good lipid profile composition. Conclusion: In conclusion, our data show that HRT has statistically significant role in determining BMI, fat percent mass and fat mass. The lipid profile including LDL, HDL, VLDL, ratio, triglycerides and total cholesterol found to be clinically better in HRT group as compared to the non-HRT group. The rationale for non-significant lipid profile probably lie in the fact that hormonal changes need a particular time period and might become significant in post-menopausal period.Keywords: body composition, hormone replacement therapy, perimenopause, women health
Procedia PDF Downloads 285802 Improving Cell Type Identification of Single Cell Data by Iterative Graph-Based Noise Filtering
Authors: Annika Stechemesser, Rachel Pounds, Emma Lucas, Chris Dawson, Julia Lipecki, Pavle Vrljicak, Jan Brosens, Sean Kehoe, Jason Yap, Lawrence Young, Sascha Ott
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Advances in technology make it now possible to retrieve the genetic information of thousands of single cancerous cells. One of the key challenges in single cell analysis of cancerous tissue is to determine the number of different cell types and their characteristic genes within the sample to better understand the tumors and their reaction to different treatments. For this analysis to be possible, it is crucial to filter out background noise as it can severely blur the downstream analysis and give misleading results. In-depth analysis of the state-of-the-art filtering methods for single cell data showed that they do, in some cases, not separate noisy and normal cells sufficiently. We introduced an algorithm that filters and clusters single cell data simultaneously without relying on certain genes or thresholds chosen by eye. It detects communities in a Shared Nearest Neighbor similarity network, which captures the similarities and dissimilarities of the cells by optimizing the modularity and then identifies and removes vertices with a weak clustering belonging. This strategy is based on the fact that noisy data instances are very likely to be similar to true cell types but do not match any of these wells. Once the clustering is complete, we apply a set of evaluation metrics on the cluster level and accept or reject clusters based on the outcome. The performance of our algorithm was tested on three datasets and led to convincing results. We were able to replicate the results on a Peripheral Blood Mononuclear Cells dataset. Furthermore, we applied the algorithm to two samples of ovarian cancer from the same patient before and after chemotherapy. Comparing the standard approach to our algorithm, we found a hidden cell type in the ovarian postchemotherapy data with interesting marker genes that are potentially relevant for medical research.Keywords: cancer research, graph theory, machine learning, single cell analysis
Procedia PDF Downloads 100801 Upconversion Nanoparticle-Mediated Carbon Monoxide Prodrug Delivery System for Cancer Therapy
Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu
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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.
Procedia PDF Downloads 106800 Microfluidic Device for Real-Time Electrical Impedance Measurements of Biological Cells
Authors: Anil Koklu, Amin Mansoorifar, Ali Beskok
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Dielectric spectroscopy (DS) is a noninvasive, label free technique for a long term real-time measurements of the impedance spectra of biological cells. DS enables characterization of cellular dielectric properties such as membrane capacitance and cytoplasmic conductivity. We have developed a lab-on-a-chip device that uses an electro-activated microwells array for loading, DS measurements, and unloading of biological cells. We utilized from dielectrophoresis (DEP) to capture target cells inside the wells and release them after DS measurement. DEP is a label-free technique that exploits differences among dielectric properties of the particles. In detail, DEP is the motion of polarizable particles suspended in an ionic solution and subjected to a spatially non-uniform external electric field. To the best of our knowledge, this is the first microfluidic chip that combines DEP and DS to analyze biological cells using electro-activated wells. Device performance is tested using two different cell lines of prostate cancer cells (RV122, PC-3). Impedance measurements were conducted at 0.2 V in the 10 kHz to 40 MHz range with 6 s time resolution. An equivalent circuit model was developed to extract the cell membrane capacitance and cell cytoplasmic conductivity from the impedance spectra. We report the time course of the variations in dielectric properties of PC-3 and RV122 cells suspended in low conductivity medium (LCB), which enhances dielectrophoretic and impedance responses, and their response to sudden pH change from a pH of 7.3 to a pH of 5.8. It is shown that microfluidic chip allowed online measurements of dielectric properties of prostate cancer cells and the assessment of the cellular level variations under external stimuli such as different buffer conductivity and pH. Based on these data, we intend to deploy the current device for single cell measurements by fabricating separately addressable N × N electrode platforms. Such a device will allow time-dependent dielectric response measurements for individual cells with the ability of selectively releasing them using negative-DEP and pressure driven flow.Keywords: microfluidic, microfabrication, lab on a chip, AC electrokinetics, dielectric spectroscopy
Procedia PDF Downloads 141799 Removal of Nickel Ions from Industrial Effluents by Batch and Column Experiments: A Comparison of Activated Carbon with Pinus Roxburgii Saw Dust
Authors: Sardar Khana, Zar Ali Khana
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Rapid industrial development and urbanization contribute a lot to wastewater discharge. The wastewater enters into natural aquatic ecosystems from industrial activities and considers as one of the main sources of water pollution. Discharge of effluents loaded with heavy metals into the surrounding environment has become a key issue regarding human health risk, environment, and food chain contamination. Nickel causes fatigue, cancer, headache, heart problems, skin diseases (Nickel Itch), and respiratory disorders. Nickel compounds such as Nickel Sulfide and Nickel oxides in industrial environment, if inhaled, have an association with an increased risk of lung cancer. Therefore the removal of Nickel from effluents before discharge is necessary. Removal of Nickel by low-cost biosorbents is an efficient method. This study was aimed to investigate the efficiency of activated carbon and Pinusroxburgiisaw dust for the removal of Nickel from industrial effluents using commercial Activated Carbon, and raw P.roxburgii saw dust. Batch and column adsorption experiments were conducted for the removal of Nickel. The study conducted indicates that removal of Nickel greatly dependent on pH, contact time, Nickel concentration, and adsorbent dose. Maximum removal occurred at pH 9, contact time of 600 min, and adsorbent dose of 1 g/100 mL. The highest removal was 99.62% and 92.39% (pH based), 99.76% and 99.9% (dose based), 99.80% and 100% (agitation time), 92% and 72.40% (Ni Conc. based) for P.roxburgii saw dust and activated Carbon, respectively. Similarly, the Ni removal in column adsorption was 99.77% and 99.99% (bed height based), 99.80% and 99.99% (Concentration based), 99.98%, and 99.81% (flow rate based) during column studies for Nickel using P.Roxburgiisaw dust and activated carbon, respectively. Results were compared with Freundlich isotherm model, which showed “r2” values of 0.9424 (Activated carbon) and 0.979 (P.RoxburgiiSaw Dust). While Langmuir isotherm model values were 0.9285 (Activated carbon) and 0.9999 (P.RoxburgiiSaw Dust), the experimental results were fitted to both the models. But the results were in close agreement with Langmuir isotherm model.Keywords: nickel removal, batch, and column, activated carbon, saw dust, plant uptake
Procedia PDF Downloads 124798 Non-Steroidal Microtubule Disrupting Analogues Induce Programmed Cell Death in Breast and Lung Cancer Cell Lines
Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron
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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.Keywords: apoptosis, autophagy, cancer, microtubule disruptor
Procedia PDF Downloads 239797 Synthesis, Characterization and Bioactivity of Methotrexate Conjugated Fluorescent Carbon Nanoparticles in vitro Model System Using Human Lung Carcinoma Cell Lines
Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam
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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate
Procedia PDF Downloads 298796 Anticancer Effect of Doxorubicin Using Injectable Hydrogel
Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim
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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection
Procedia PDF Downloads 399795 Development of Composition and Technology of Vincristine Nanoparticles Using High-Molecular Carbohydrates of Plant Origin
Authors: L. Ebralidze, A. Tsertsvadze, D. Berashvili, A. Bakuridze
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Current cancer therapy strategies are based on surgery, radiotherapy and chemotherapy. The problems associated with chemotherapy are one of the biggest challenges for clinical medicine. These include: low specificity, broad spectrum of side effects, toxicity and development of cellular resistance. Therefore, anti-cance drugs need to be develop urgently. Particularly, in order to increase efficiency of anti-cancer drugs and reduce their side effects, scientists work on formulation of nano-drugs. The objective of this study was to develop composition and technology of vincristine nanoparticles using high-molecular carbohydrates of plant origin. Plant polysacharides, particularly, soy bean seed polysaccharides, flaxseed polysaccharides, citrus pectin, gum arabic, sodium alginate were used as objects. Based on biopharmaceutical research, vincristine containing nanoparticle formulations were prepared. High-energy emulsification and solvent evaporation methods were used for preparation of nanosystems. Polysorbat 80, polysorbat 60, sodium dodecyl sulfate, glycerol, polyvinyl alcohol were used in formulation as emulsifying agent and stabilizer of the system. The ratio of API and polysacharides, also the type of the stabilizing and emulsifying agents are very effective on the particle size of the final product. The influence of preparation technology, type and concentration of stabilizing agents on the properties of nanoparticles were evaluated. For the next stage of research, nanosystems were characterized. Physiochemical characterization of nanoparticles: their size, shape, distribution was performed using Atomic force microscope and Scanning electron microscope. The present study explored the possibility of production of NPs using plant polysaccharides. Optimal ratio of active pharmaceutical ingredient and plant polysacharids, the best stabilizer and emulsifying agent was determined. The average range of nanoparticles size and shape was visualized by SEM.Keywords: nanoparticles, target delivery, natural high molecule carbohydrates, surfactants
Procedia PDF Downloads 265794 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification
Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou
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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms
Procedia PDF Downloads 244793 Cosmetic Value of Collatamp in Breast Conserving Surgery
Authors: Chee Young Kim, Tae Hyun Kim, Anbok Lee, Hyun-Ah Kim, Woosung Lim, Ku Sang Kim, Jinsun Lee, Yoo Seok Kim, Beom Seok Ko
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Background: CollatampTM is Gentamicin-containing collagen sponge well known for its hemostatic effect, commonly utilized in surgeries. We inserted CollatempTM wrapped by SurgicelTM (oxidized cellulose polymer) to fill up the defect after breast conserving surgery. The purpose of this study is to verify the furthermore cosmetic value of CollatampTM in breast conserving surgery conducted in breast cancer patients. Methods: 17 patients were enrolled in this study, underwent breast conserving surgery with CollatampTM wrapped by SurgicelTM insertion, in Inje University Busan Paik Hospital from October 2015 to September 2016. Patient satisfaction, cosmetic outcome, results at 6 months from operation was analyzed to verify the effectiveness and usefulness of CollatampTM for cosmetics. Patient satisfaction was investigated through interviews on a scale of good, fair, poor, and the cosmetic outcome was investigated through physical examination by a surgeon who did not participate in the operations. Results: Among 17 patients, nine of them gave ‘good’ for patient satisfaction, eight gave ‘fair’ and none of them ‘poor’. Also, cosmetic outcome came out with 11 ‘good’s, six ‘fair’s, no ‘poor’. In ‘good’ patient satisfaction group, the mean value of resection to breast volume ratio was 16%, compared to 24% of ‘fair’ group. The mean value of actual resection volume was 100.6cm3, 102.7cm3 each. In ‘good’ cosmetic outcome group, the mean value of resection to breast volume ratio was 18%, compared to 23% of ‘fair’ group. The mean value of actual resection volume was 99.2cm3, 105.9cm3 respectively. According to these results, patient satisfaction and cosmetic outcome after surgeries were more reliable on the resection to breast volume ratio, rather than the actual resection volume. There were eight cases of postoperative complications, consisting of a lymphedema, a seroma, and six patients had mild pain. Conclusions: Cosmetic effect of CollatampTM in breast conserving surgery was more reliable on the resection to breast volume ratio, rather than the actual resection volume. In this short term survey, patients were tend to be satisfied with the cosmetics, all giving either good or fair scores. However, long term outcomes should be further assessed.Keywords: breast cancer, breast conserving surgery, collatamp, cosmetics
Procedia PDF Downloads 250792 Ficus Microcarpa Fruit Derived Iron Oxide Nanomaterials and Its Anti-bacterial, Antioxidant and Anticancer Efficacy
Authors: Fuad Abdullah Alatawi
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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity
Procedia PDF Downloads 109791 Automatic Identification of Pectoral Muscle
Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina
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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle
Procedia PDF Downloads 342790 Quality of Life in People with Hearing Loss: A Study of Patients Referred to an Audiological Service
Authors: Peder O. Laugen Heggdal, Oyvind Nordvik, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad
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Background: Hearing loss (HL) affect people of all ages and stages in life. To author's best knowledge, if patients with an HL have reduced Generic Quality of life (QoL), has yet not been answered. Aim: The aim of the present study was to investigate the relationship between HL and generic and disease-specific Health Related Quality of Life (HRQoL) in adult patients (aged 18–78 years) with an HL, seeking Hearing Aid (HA). Material and Methods: 158 adult (aged 18-78 years) patients with HL, referred for HA fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals, were included. First-time users had been pre-examined by an Ear Nose and Throat specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2 and 4 kHz) was determined for each ear. The generic European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire general part and a shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) were answered. In addition, EORTC HRQoL answers from a general population and patients with former head and neck cancer served as comparison. Results: In general, no lowered HRQoL scores were determined among HL patients compared to the general population. Patients with unilateral HL to some extent showed lower HRQoL than those with bilateral HL (social function and fatigue). The APHAB scores correlated significantly with the EORTC HRQoL scores. By stepwise linear regression analysis, the APHAB scores were scored secondary to PTA (best ear), cognitive and physical function. Conclusion: HRQoL scores in HL patients, in general, seems to be at the population level, but the unilateral HL patients scored to some extent lower than the bilateral HI patients. APHAB and generic QoL scores levels are associated. Both HRQoL and APHAB scores are generated more complexly than anticipated.Keywords: quality of life, hearing loss, hearing impairment, distress, depression, anxiety, hearing aid
Procedia PDF Downloads 281789 Synthesis, Characterization and Biological Properties of Half-Sandwich Complexes of Ruthenium(II), Rhodium(II) and Iridium(III)
Authors: A. Gilewska, J. Masternak, K. Kazimierczuk, L. Turlej, J. Wietrzyk, B. Barszcz
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Platinum-based drugs are now widely used as chemotherapeutic agents. However the platinum complexes show the toxic side-effects: i) the development of platinum resistance; ii) the occurrence of severe side effects, such as nephro-, neuro- and ototoxicity; iii) the high toxicity towards human fibroblast. Therefore the development of new anticancer drugs containing different transition-metal ions, for example, ruthenium, rhodium, iridium is a valid strategy in cancer treatment. In this paper, we reported the synthesis, spectroscopic, structural and biological properties of complexes of ruthenium, rhodium, and iridium containing N,N-chelating ligand (2,2’-bisimidazole). These complexes were characterized by elemental analysis, UV-Vis and IR spectroscopy, X-ray diffraction analysis. These complexes exhibit a typical pseudotetrahedral three-legged piano-stool geometry, in which the aromatic arene ring forms the seat of the piano-stool, while the bidentate 2,2’-bisimidazole (ligand) and the one chlorido ligand form the three legs of the stool. The spectroscopy data (IR, UV-Vis) and elemental analysis correlate very well with molecular structures. Moreover, the cytotoxic activity of the complexes was carried out on human cancer cell lines: LoVo (colorectal adenoma), MV-4-11 (myelomonocytic leukaemia), MCF-7 (breast adenocarcinoma) and normal healthy mouse fibroblast BALB/3T3 cell lines. To predict a binding mode, a potential interaction of metal complexes with calf thymus DNA (CT-DNA) and protein (BSA) has been explored using UV absorption and circular dichroism (CD). It is interesting to note that the investigated complexes show no cytotoxic effect towards the normal BALB/3T3 cell line, compared to cisplatin, which IC₅₀ values was determined as 2.20 µM. Importantly, Ru(II) displayed the highest activity against HL-60 (IC₅₀ 4.35 µM). The biological studies (UV-Vis and circular dichroism) suggest that arene-complexes could interact with calf thymus DNA probably via an outside binding mode and interact with protein (BSA).Keywords: ruthenium(II) complex, rhodium(III) complex, iridium(III) complex, biological activity
Procedia PDF Downloads 122788 Next Generation Radiation Risk Assessment and Prediction Tools Generation Applying AI-Machine (Deep) Learning Algorithms
Authors: Selim M. Khan
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Indoor air quality is strongly influenced by the presence of radioactive radon (222Rn) gas. Indeed, exposure to high 222Rn concentrations is unequivocally linked to DNA damage and lung cancer and is a worsening issue in North American and European built environments, having increased over time within newer housing stocks as a function of as yet unclear variables. Indoor air radon concentration can be influenced by a wide range of environmental, structural, and behavioral factors. As some of these factors are quantitative while others are qualitative, no single statistical model can determine indoor radon level precisely while simultaneously considering all these variables across a complex and highly diverse dataset. The ability of AI- machine (deep) learning to simultaneously analyze multiple quantitative and qualitative features makes it suitable to predict radon with a high degree of precision. Using Canadian and Swedish long-term indoor air radon exposure data, we are using artificial deep neural network models with random weights and polynomial statistical models in MATLAB to assess and predict radon health risk to human as a function of geospatial, human behavioral, and built environmental metrics. Our initial artificial neural network with random weights model run by sigmoid activation tested different combinations of variables and showed the highest prediction accuracy (>96%) within the reasonable iterations. Here, we present details of these emerging methods and discuss strengths and weaknesses compared to the traditional artificial neural network and statistical methods commonly used to predict indoor air quality in different countries. We propose an artificial deep neural network with random weights as a highly effective method for assessing and predicting indoor radon.Keywords: radon, radiation protection, lung cancer, aI-machine deep learnng, risk assessment, risk prediction, Europe, North America
Procedia PDF Downloads 87787 Characterization of Transmembrane Proteins with Five Alpha-Helical Regions
Authors: Misty Attwood, Helgi Schioth
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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein
Procedia PDF Downloads 103786 Formulation, Preparation, and Evaluation of Coated Desloratadine Oral Disintegrating Tablets
Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada
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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking
Procedia PDF Downloads 448785 Biodegradable Polymeric Vesicles Containing Magnetic Nanoparticles, Quantum Dots and Anticancer Drugs for Drug Delivery and Imaging
Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan
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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 463