Search results for: cancer survivor

Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

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Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

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Authors: Suhas Pednekar, Prashant Chavan, Ramesh Chaughule, Deepak Patkar

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Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) are one of the most attractive nanomaterials for various biomedical applications. An important potential medical application of polymer-coated iron oxide nanoparticles (NPs) is as imaging agents. Composition, size, morphology and surface chemistry of these nanoparticles can now be tailored by various processes to not only improve magnetic properties but also affect the behavior of nanoparticles in vivo. MNPs are being actively investigated as the next generation of magnetic resonance imaging (MRI) contrast agents. Also, there is considerable interest in developing magnetic nanoparticles and their surface modifications with therapeutic agents. Our study involves the synthesis of biocompatible cancer drug coated with iron oxide nanoparticles and to evaluate their efficacy as MRI contrast agents. A simple and rapid microwave method to prepare Fe3O4 nanoparticles has been developed. The drug was successfully conjugated to the Fe3O4 nanoparticles which can be used for various applications. The relaxivity R2 (reciprocal of the spin-spin relaxation time T2) is an important factor to determine the efficacy of Fe nanoparticles as contrast agents for MRI experiments. R2 values of the coated magnetic nanoparticles were also measured using MRI technique and the results showed that R2 of the Fe complex consisting of Fe3O4, polymer and drug was higher than that of bare Fe nanoparticles and polymer coated nanoparticles. This is due to the increase in hydrodynamic sizes of Fe NPs. The results with various amounts of iron molar concentrations are also discussed. Using MRI, it is seen that the R2 relaxivity increases linearly with increase in concentration of Fe NPs in water.

Keywords: cancer drug, hydrodynamic size, magnetic nanoparticles, MRI

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Authors: Alex Hughes

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Patients with advanced heart failure develop specific palliative care needs due to the progressive symptom burden and unpredictable disease trajectory. NICE guidance advises that palliative care should be provided to patients with both cancer and non-cancer conditions as and when required. However, there is some way to go before this guidance is consistently and effectively implemented nationwide in conditions such as heart failure. The Ambitions for Palliative and End of Life Care: A national framework for local action in England provides a set of foundations and ambitions which outline a vision for what high-quality palliative and end-of-life care look like in England. This poster aims to critically consider how to improve access to palliative care for heart failure patients in England by analysing the foundations taken from this framework to generate specific recommendations using Soft Systems Methodology (SSM). The eight foundations analysed are: ‘Personalised care planning’, ‘Shared records’, ‘Evidence and information’, ‘Involving, supporting and caring for those important to the dying Person’, ‘Education and training’, ‘24/7 access’, ‘Co-design’ and ‘Leadership.’ A number of specific recommendations have been generated which highlight a need to close the evidence-policy gap and implement policy with sufficient evidence. These recommendations, alongside the creation of an evidence-based national strategy for palliative care and heart failure, should improve access to palliative care for heart failure patients in England. Once implemented, it will be necessary to evaluate the effect of these proposals to understand if access to palliative care for heart failure patients actually improves.

Keywords: access, health systems, heart failure, palliative care

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Authors: Yao Song, Danni Cheng, Jianjun Ren

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Objectives: We aimed to explore the prognostic effects of absolute values and dynamic changes of common hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients treated with radiation. Methods and materials: The absolute values of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline (within 45 days before radiation), 1-, 3-, 6- and 12-months after the start of radiotherapy were retrospectively collected. Locally-estimated smoothing scatterplots were used to describe the smooth trajectory of each index. A mixed-effect model with a random slope was fitted to describe the changing rate and trend of indices over time. Cox proportional hazard analysis was conducted to assess the correlation between hematological indices and treatment outcomes. Results: Of the enrolled 85 OPSCC patients, inflammatory indices, such as WBC and ALC, dropped rapidly during acute treatment and gradually recovered, while NLR and PLR increased at first three months and subsequently declined within 3-12 months. Higher absolute value or increasing trend of nutritional indices (Alb and Hb) was associated with better prognosis (all p<0.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (WBC, ANC, Plt, PLR and NLR) had worse survival (all p<0.05). Conclusions: The absolute values and dynamic changes of hematological indices were valuable prognostic factors for OPSCC patients who underwent radiotherapy.

Keywords: hematological indices, oropharyngeal cancer, radiotherapy, NLR, PLR

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Authors: Harish Rajak, Preeti Patel

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The application of histone deacetylase inhibitors is a well-known strategy in prevention of cancer which shows acceptable preclinical antitumor activity due to its ability of growth inhibition and apoptosis induction of cancer cell. Molecular docking were performed using Histone Deacetylase protein (PDB ID:1t69) and prepared series of hydroxamic acid based HDACIs. On the basis of docking study, it was predicted that compound 1 has significant binding interaction with HDAC protein and three hydrogen bond interactions takes place, which are essential for antitumor activity. On docking, most of the compounds exhibited better glide score values between -8 to -10 which is close to the glide score value of suberoylanilide hydroxamic acid. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. The 3D-QSAR models provided a good correlation between predicted and actual anticancer activity. Best QSAR model showed Q2 (0.7974), R2 (0.9200) and standard deviation (0.2308). QSAR visualization maps suggest that hydrogen bond acceptor groups at carbonyl group of cap region and hydrophobic groups at ortho, meta, para position of R9 were favorable for HDAC inhibitory activity. We established structure activity correlation using docking, pharmacophore modeling and atom based 3D QSAR model for hydroxamic acid based HDACIs.

Keywords: HDACIs, QSAR, e-pharmacophore, docking, suberoylanilide hydroxamic acid

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Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

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Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

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Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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Authors: Zerrin Akter Anni

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The media's role in shaping perceptions of violence against women (VAW) and their portrayal in news reporting significantly influences our understanding of this critical issue. My research delves into the portrayal of violence against women in mainstream media, using the prominent case of Dr. Rumana Manzur, a former UBC Fulbright Scholar from Bangladesh who suffered a brutal assault by her ex-husband in June 2011. Employing a qualitative research approach, this study uses an ethnographic media analysis method to scrutinize news reports of the aforementioned case from selected newspapers in Bangladesh. The primary objectives are to investigate how the popular news media in Bangladesh addresses the issue of violence against women and frames the victims of such violence. The findings of this research highlight that news media can perpetuate gender stereotypes and subtly shift blame onto the victim through various techniques, creating intricate interactions between the reader and the text. These techniques include sensationalized headlines, textual content, and graphic images. This victim-blaming process not only retraumatizes the survivor but also distorts the actual facts when presenting the case to a larger audience. Consequently, the representation of violence against women cases in media, particularly the portrayal of women as victims during reporting, significantly impacts our collective comprehension of this issue. In conclusion, this paper asserts that the Bangladeshi media, particularly news outlets, in conjunction with society, continue to follow a pattern of depicting gender-based violence in ways that devalue the image of women. This research underscores the need for critical analysis of media representations of violence against women cases, as they can perpetuate harmful stereotypes and hinder efforts to combat this pervasive problem. Therefore, the outcome of this research is to comprehend the complex dynamics between media and violence against women, which is essential for fostering a more empathetic and informed society that actively works towards eradicating this problem from our society.

Keywords: media representation, violence against women (vaw), ethnographic media analysis, victim-blaming, sensationalized headline

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Authors: Jayanti Gyawali, Deepak Adhikari, Mukesh Mallik, Sanjay Sah

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Radiation is defined as an emission or transmission of energy in form of waves or particles through space or material medium. The major imaging tools used in diagnostic radiology is based on the use of ionizing radiation. A cross-sectional study was carried out during July- August, 2015 among technicians in 15 different hospitals of Bharatpur, Chitwan, Nepal to assess awareness regarding radiation protection and their current practice. The researcher was directly engaged for data collection using self-administered semi-structured questionnaire. The findings of the study are presented in socio-demographic characteristics of respondents, current practice of respondents and knowledge regarding radiation protection. The result of this study demonstrated that despite the importance of radiation and its consequent hazards, the level of knowledge among technicians is only 60.23% and their current practice is 76.84%. The difference in the mean score of knowledge and practice might have resulted due to technicians’s regular work and lack of updates. The study also revealed that there is no significant (p>0.05) difference in knowledge level of technicians practicing in different hospitals. But the mean difference in practice scores of different hospital is significant (p<0.05) i.e. i.e. the cancer hospital with large volumes of regular radiological cases and radiation therapies for cancer treatment has better practice in comparison to other hospitals. The deficiency in knowledge of technicians might alter the expected benefits, compared to the risk involved, and can cause erroneous medical diagnosis and radiation hazard. Therefore, this study emphasizes the need for all technicians to update themselves with the appropriate knowledge and current practice about ionizing and non-ionizing radiation.

Keywords: technicians, knowledge, Nepal, radiation

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Authors: Mitchell T. Grothaus, Cory Grigsby, Timothy S. Hare

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This study aims to determine if there is a relationship between elevated cancer risks in eastern Kentucky and the environmental effects of black shale. Previous research shows that black shale formations, such as those in eastern Kentucky contain high levels of toxic elements including arsenic and radon compared to average rocks and sediment. Similarly, the population of eastern Kentucky has higher rates of many health conditions, including lung cancer and cardiovascular disease, than surrounding regions. These poor health outcomes are typically explained in relation to social, economic, behavioral, and healthcare factors. The rates of many conditions, however, have not decreased as these factors improve with regional development. Black shale is known to affect environmental conditions such as by increasing radiation levels and heavy metal toxicity. We are mapping the effects of black shale through monitoring radiation, microbes, and chemical standards of water sources. In this presentation, we report on our measuring pH, dissolved oxygen, total dissolved solids, conductivity, temperature, and discharge and comparison with water quality standards from the Kentucky Department for Environmental Protection. The conditions of water sources combined with an environmental survey of the surrounding areas provide a greater understanding of why the people in eastern Kentucky face the current health issues.

Keywords: black shale, eastern Kentucky, environmental impact, water quality

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Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

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Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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Authors: Andy Ho

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Breast cancer is a common cancer in Australia. Early diagnosis is crucial for improving patient outcomes, as later-stage detection correlates with poorer prognoses. While multiparametric MRI offers superior sensitivity in detecting invasive and high-grade breast cancers compared to conventional mammography, its extended scan duration and high costs limit widespread application. As a result, full protocol MRI screening is typically reserved for patients at elevated risk. Recent advancements in imaging technology have facilitated the development of Abbreviated MRI protocols, which dramatically reduce scan times (<10 minutes compared to >30 minutes for full protocol). The potential for Abbreviated MRI to offer a more time- and cost-efficient alternative has implications for improving patient accessibility, reducing appointment durations, and enhancing compliance—especially relevant for individuals requiring regular annual screening over several decades. The purpose of this study is to assess the diagnostic efficacy of Abbreviated MRI for breast cancer screening among high-risk patients at the Royal Prince Alfred Hospital (RPA). This study aims to determine the sensitivity, specificity, and inter-reader variability of Abbreviated MRI protocols when interpreted by subspecialty-trained Breast Radiologists. A systematic review of the RPA’s electronic Picture Archive and Communication System identified high-risk patients, defined by Australian ‘Medicare Benefits Schedule’ criteria, who underwent Breast MRI from 2021 to 2022. Eligible participants included asymptomatic patients under 50 years old referred by the High-Risk Clinic due to a high-risk genetic profile or relevant familial history. The MRIs were anonymized, randomized, and interpreted by four Breast Radiologists, each independently completing standardized proforma evaluations. Radiological findings were compared against histopathology as the gold standard or follow-up imaging if biopsies were unavailable. Statistical metrics, including sensitivity, specificity, and inter-reader variability, were assessed. The Fleiss-Kappa analysis demonstrated a fair inter-reader agreement (kappa = 0.25; 95% CI: 0.19–0.32; p < 0.0001). The sensitivity for detecting malignancies was 0.75, with a specificity of 0.84. These findings underline the potential of Abbreviated MRI as a reliable screening tool for malignancies with significant specificity, though reduced sensitivity highlights the importance of robust radiologist training and consistent evaluation standards. Abbreviated MRI protocols exhibit promise as a viable screening option for high-risk patients, combining reduced scan times and acceptable diagnostic accuracy. Further work to refine interpretation practices and optimize training is essential to maximize the protocol’s utility in routine clinical screening and facilitate broader accessibility.

Keywords: abbreviated, breast, cancer, MRI

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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Authors: Mónica P. Cala, Juan S. Carreño, Roland J.W. Meesters

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Recently, collection of biological fluids on special filter papers has become a popular micro-sampling technique. Especially, the dried blood spot (DBS) micro-sampling technique has gained much attention and is momently applied in various life sciences reserach areas. As a result of this popularity, DBS are not only intensively competing with the venous blood sampling method but are at this moment widely applied in numerous bioanalytical assays. In particular, in the screening of inherited metabolic diseases, pharmacokinetic modeling and in therapeutic drug monitoring. Recently, microsampling techniques were also introduced in “omics” areas, whereunder metabolomics. For a metabolic profiling study we applied micro-sampling of biological fluids (blood and plasma) from healthy controls and from women with breast cancer. From blood samples, dried blood and plasma samples were prepared by spotting 8uL sample onto pre-cutted 5-mm paper disks followed by drying of the disks for 100 minutes. Dried disks were then extracted by 100 uL of methanol. From liquid blood and plasma samples 40 uL were deproteinized with methanol followed by centrifugation and collection of supernatants. Supernatants and extracts were evaporated until dryness by nitrogen gas and residues derivated by O-methyxyamine and MSTFA. As internal standard C17:0-methylester in heptane (10 ppm) was used. Deconvolution and alignment of and full scan (m/z 50-500) MS data were done by AMDIS and SpectConnect (http://spectconnect.mit.edu) software, respectively. Statistical Data analysis was done by Principal Component Analysis (PCA) using R software. The results obtained from our preliminary study indicate that the use of dried blood/plasma on paper disks could be a powerful new tool in metabolic profiling. Many of the metabolites observed in plasma (liquid/dried) were also positively identified in whole blood samples (liquid/dried). Whole blood could be a potential substitute matrix for plasma in Metabolomic profiling studies as well also micro-sampling techniques for the collection of samples in clinical studies. It was concluded that the separation of the different sample methodologies (liquid vs. dried) as observed by PCA was due to different sample treatment protocols applied. More experiments need to be done to confirm obtained observations as well also a more rigorous validation .of these micro-sampling techniques is needed. The novelty of our approach can be found in the application of different biological fluid micro-sampling techniques for metabolic profiling.

Keywords: biofluids, breast cancer, metabolic profiling, micro-sampling

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Authors: Geir Kirkebøen

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Most patients with serious diagnoses want to know their prognosis, in particular their expected survival time. As part of the informed consent process, physicians are legally obligated to communicate such information to patients. However, there is no established (evidence based) ‘best practice’ for how to do this. The two questions explored in this study are: How do physicians communicate expected survival time to patients, and how should it be done? We explored the first, descriptive question in a study with Norwegian oncologists as participants. The study had a scenario and a survey part. In the scenario part, the doctors should imagine that a patient, recently diagnosed with a serious cancer diagnosis, has asked them: ‘How long can I expect to live with such a diagnosis? I want an honest answer from you!’ The doctors should assume that the diagnosis is certain, and that from an extensive recent study they had optimal statistical knowledge, described in detail as a right-skewed survival curve, about how long such patients with this kind of diagnosis could be expected to live. The main finding was that very few of the oncologists would explain to the patient the variation in survival time as described by the survival curve. The majority would not give the patient an answer at all. Of those who gave an answer, the typical answer was that survival time varies a lot, that it is hard to say in a specific case, that we will come back to it later etc. The survey part of the study clearly indicates that the main reason why the oncologists would not deliver the mortality prognosis was discomfort with its uncertainty. The scenario part of the study confirmed this finding. The majority of the oncologists explicitly used the uncertainty, the variation in survival time, as a reason to not give the patient an answer. Many studies show that patients want realistic information about their mortality prognosis, and that they should be given hope. The question then is how to communicate the uncertainty of the prognosis in a realistic and optimistic – hopeful – way. Based on psychological research, our hypothesis is that the best way to do this is by explicitly describing the variation in survival time, the (usually) right skewed survival curve of the prognosis, and emphasize to the patient the (small) possibility of being a ‘lucky outlier’. We tested this hypothesis in two scenario studies with lay people as participants. The data clearly show that people prefer to receive expected survival time as a median value together with explicit information about the survival curve’s right skewedness (e.g., concrete examples of ‘positive outliers’), and that communicating expected survival time this way not only provides people with hope, but also gives them a more realistic understanding compared with the typical way expected survival time is communicated. Our data indicate that it is not the existence of the uncertainty regarding the mortality prognosis that is the problem for patients, but how this uncertainty is, or is not, communicated and explained.

Keywords: cancer patients, decision psychology, doctor-patient communication, mortality prognosis

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Authors: Shiva Rezaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri, Mehryar Zargari

Abstract:

Objective(s): Cyclophosphamide (CP), as an antineoplastic drug, is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA), as a natural phenylpropanoid, has antioxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Keywords: apoptosis, cyclophosphamide, liver injury, inflammation, oxidative stress, sinapic acid

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Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

Abstract:

After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

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Authors: S. Zith Dey Babu, S. Kour, S. Verma, C. Verma, V. Pathania, A. Agrawal, V. Chaudhary, A. Manoj Puthur, R. Goyal, A. Pal, T. Danti Dey, A. Kumar, K. Wadhwa, O. Ved

Abstract:

Background: Skin cancer is now is the buzzing button in the field of medical science. The cyst's pandemic is drastically calibrating the body and well-being of the global village. Methods: The extracted image of the skin tumor cannot be used in one way for diagnosis. The stored image contains anarchies like the center. This approach will locate the forepart of an extracted appearance of skin. Partitioning image models has been presented to sort out the disturbance in the picture. Results: After completing partitioning, feature extraction has been formed by using genetic algorithm and finally, classification can be performed between the trained and test data to evaluate a large scale of an image that helps the doctors for the right prediction. To bring the improvisation of the existing system, we have set our objectives with an analysis. The efficiency of the natural selection process and the enriching histogram is essential in that respect. To reduce the false-positive rate or output, GA is performed with its accuracy. Conclusions: The objective of this task is to bring improvisation of effectiveness. GA is accomplishing its task with perfection to bring down the invalid-positive rate or outcome. The paper's mergeable portion conflicts with the composition of deep learning and medical image processing, which provides superior accuracy. Proportional types of handling create the reusability without any errors.

Keywords: computer-aided system, detection, image segmentation, morphology

Procedia PDF Downloads 150

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

Procedia PDF Downloads 63

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

Procedia PDF Downloads 62

Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

Abstract:

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

Procedia PDF Downloads 108

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Elham Mansouri, Asghar Mesbahi

Abstract:

Purpose: In the current study, we aimed to investigate the macroscopic and microscopic dose enhancement effect of metallic nanoparticles in interstitial brachytherapy of uterus cancer by Iodin-125 source using a nano-lattice model in MCNPX (5) and MCNP6.1 codes. Materials and methods: Based on a nano-lattice simulation model containing a radiation source and a tumor tissue with cellular compartments loaded with 7mg/g spherical nanoparticles (bismuth, gold, and gadolinium), the energy deposited by the secondary electrons in microscopic and macroscopic level was estimated. Results: The results show that the values of macroscopic DEF is higher than microscopic DEF values and the macroscopic DEF values decreases as a function of distance from the brachytherapy source surface. Also, the results revealed a remarkable discrepancy between the DEF and secondary electron spectra calculated by MCNPX (5) and MCNP6.1 codes, which could be justified by the difference in energy cut-off and electron transport algorithms of two codes. Conclusion: According to the both MCNPX (5) and MCNP6.1 outputs, it could be concluded that the presence of metallic nanoparticles in the tumor tissue of uteruscancer increases the physical effectiveness of brachytherapy by I-125 source. The results presented herein give a physical view of radiosensitization potential of different metallic nanoparticles and could be considered in design of analytical and experimental radiosensitization studies in tumor regions using various radiotherapy modalities in the presence of heavy nanomaterials.

Keywords: MCNPX, MCNP6, nanoparticle, brachytherapy

Procedia PDF Downloads 102

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

Abstract:

Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

Procedia PDF Downloads 97

Authors: Sarah A. Alotaibi, Mohammed A. Almutairi, Abdullah A. Alsayari, Adibah M. Almutairi, Somaiah K. Almubayedh

Abstract:

Concerns over the presence of acrylamide in food date back to 2002, when Swedish scientists stated that, in carbohydrate-rich foods, amounts of acrylamide were formed when cooked at high temperatures. Similar findings were reported by other researchers which, consequently, caused major international efforts to investigate dietary exposure and the subsequent health complications in order to properly manage this issue. Due to this issue, in this work, we aim to determine the acrylamide level in different foods (coffee, potato chips, biscuits, and baby food) commonly consumed by the Saudi population. In a total of forty-three samples, acrylamide was detected in twenty-three samples at levels of 12.3 to 2850 µg/kg. In reference to the food groups, the highest concentration of acrylamide was found in coffee samples (<12.3-2850 μg/kg), followed by potato chips (655-1310 μg/kg), then biscuits (23.5-449 μg/kg), whereas the lowest acrylamide level was observed in baby food (<14.75 – 126 μg/kg). Most coffee, biscuits and potato chips products contain high amount of acrylamide content and also the most commonly consumed product. Saudi adults had a mean exposure of acrylamide for coffee, potato, biscuit, and cereal (0.07439, 0.04794, 0.01125, 0.003371 µg/kg-b.w/day), respectively. On the other hand, exposure to acrylamide in Saudi infants and children to the same types of food was (0.1701, 0.1096, 0.02572, 0.00771 µg/kg-b.w/day), respectively. Most groups have a percentile that exceeds the tolerable daily intake (TDI) cancer value (2.6 µg/kg-b.w/day). Overall, the MOE results show that the Saudi population is at high risk of acrylamide-related disease in all food types, and there is a chance of cancer risk in all age groups (all values ˂10,000). Furthermore, it was found that in non-cancer risks, the acrylamide in all tested foods was within the safe limit (˃125), except for potato chips, in which there is a risk for diseases in the population. With potato and coffee as raw materials, additional studies were conducted to assess different factors, including temperature, cocking time, and additives affecting the acrylamide formation in fried potato and roasted coffee, by systematically varying processing temperatures and time values, a mitigation of acrylamide content was achieved when lowering the temperature and decreasing the cooking time. Furthermore, it was shown that the combination of the addition of chitosan and NaCl had a large impact on the formation.

Keywords: risk assessment, dietary exposure, MOA, acrylamide, hazard

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Authors: Somit Dutta, Pallab Kar, Arnab Kumar Chakraborty, Arnab Sen, Tapas Kumar Chaudhuri

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In the present study three species of Clerodendrum; Clerodendrum indicum, Volkameria inermis and Clerodendrum colebrookianum were used to investigate the possible activity against oxidative stress. A detailed in-vivo and in-vitro antioxidant profiling, directly associated with inflammation-related carcinogenesis, has been executed with a motive to evaluate the free radical scavenging activity of Clerodendrum extract. Measurement of cell viability and ROS generation in HEK-293 (Human Embryonic Kidney Cell Line) cells was also estimated. The immune cell proliferative properties (MTT) and in-vitro assay for evaluation of their antioxidant activities including hydroxyl radical, nitric oxide, singlet oxygen, peroxinitrate and hydrogen peroxide, etc. were investigated. GC-MS and FTIR analyses have been performed to identify the active biological compounds. These active biological compounds were further studied to assess their potential medicinal properties, aided by molecular docking and interaction analysis between the active compounds and different proteins related to oxidative stress leading to progression of carcinogenesis. The research article clearly demonstrates the role of ROS in various phases of carcinogenesis. Therefore, the antioxidant and free radical scavenging capacity of all the Clerodendrum species might prove beneficial for the immune system. It might be concluded that this plant species offers great promise for cancer prevention and therapy due to the presence of several bioactive compounds and potent antioxidant capacity of C. colebrookianum.

Keywords: antioxidant, cancer, oxidative stress, reactive oxygen species (ROS)

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

Abstract:

MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

Procedia PDF Downloads 167

Authors: Puneet Goyal, Aarti Agarwal

Abstract:

Background and Objective: Nutritional support is an integral part of palliative care of advanced non-resectable abdominal malignancy patients, though is frequently neglected aspect. Non-Healing high output Entero-cutaneous fistulas sometimes require long term parenteral nutrition, to take care of catabolism and replacement of nutrients. We present a case of inoperable pancreatic malignancy with high output entero-cutaneous fistula, which was provided parenteral nutritional support with the use of Totally Implantable Venous Access Device (TIVAD). Method and Results: 55 year old man diagnosed with carcinoma pancreas had developed high entero-cutaneous fistula. His tumor was found to be inoperable and was on total parenteral nutrition through routine central line. This line was difficult to maintain as he required it for a long term TPN. He was planned to undergo Totally Implantable Venous Access Device (TIVAD) implantation. 8Fr single lumen catheter with Groshong non-return Valve (Bard Access Systems, Inc. USA) was inserted through right internal jugular vein, under fluoroscopic guidance. The catheter was tunneled subcutaneously and brought towards infraclavicular pocket, cut at appropriate length and connected to port and locked. Port was sutured in floor of pocket. Free flow of blood aspirated, flushed with heparinized saline. There was no kink observed in entire length of catheter under fluoroscopy. Skin over infraclavicular pocket was sutured. Long term catheter care and associated risks were explained to patient and relatives. Patient continued to receive total parenteral nutrition as well as other supportive therapy though TIVAD for next 6 weeks, till his demise. Conclusion: TIVADs are standard of care for long term venous access solutions in cancer patients requiring chemotherapy. In this case, we extended its use for providing parenteral nutrition and other supportive therapy. TIVADs can be implanted in advanced cancer patients for providing venous access solution required for various palliative treatments and medications. This will help in improving quality of life and satisfaction amongst terminally ill cancer patients.

Keywords: parenteral nutrition, totally implantable venous access device, long term venous access, interventions in anesthesiology

Procedia PDF Downloads 247