Search results for: metastatic breast cancer
537 Potential Activities of Human Endogenous Retroviral kDNA in Melanoma Pathogenesis and HIV-1 Infection
Authors: Jianli Dong, Fangling Xu, Gengming Huang
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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.Keywords: CD4 cell, HERV-K, HIV-1, melanoma
Procedia PDF Downloads 232536 Characterizing and Developing the Clinical Grade Microbiome Assay with a Robust Bioinformatics Pipeline for Supporting Precision Medicine Driven Clinical Development
Authors: Danyi Wang, Andrew Schriefer, Dennis O'Rourke, Brajendra Kumar, Yang Liu, Fei Zhong, Juergen Scheuenpflug, Zheng Feng
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Purpose: It has been recognized that the microbiome plays critical roles in disease pathogenesis, including cancer, autoimmune disease, and multiple sclerosis. To develop a clinical-grade assay for exploring microbiome-derived clinical biomarkers across disease areas, a two-phase approach is implemented. 1) Identification of the optimal sample preparation reagents using pre-mixed bacteria and healthy donor stool samples coupled with proprietary Sigma-Aldrich® bioinformatics solution. 2) Exploratory analysis of patient samples for enabling precision medicine. Study Procedure: In phase 1 study, we first compared the 16S sequencing results of two ATCC® microbiome standards (MSA 2002 and MSA 2003) across five different extraction kits (Kit A, B, C, D & E). Both microbiome standards samples were extracted in triplicate across all extraction kits. Following isolation, DNA quantity was determined by Qubit assay. DNA quality was assessed to determine purity and to confirm extracted DNA is of high molecular weight. Bacterial 16S ribosomal ribonucleic acid (rRNA) amplicons were generated via amplification of the V3/V4 hypervariable region of the 16S rRNA. Sequencing was performed using a 2x300 bp paired-end configuration on the Illumina MiSeq. Fastq files were analyzed using the Sigma-Aldrich® Microbiome Platform. The Microbiome Platform is a cloud-based service that offers best-in-class 16S-seq and WGS analysis pipelines and databases. The Platform and its methods have been extensively benchmarked using microbiome standards generated internally by MilliporeSigma and other external providers. Data Summary: The DNA yield using the extraction kit D and E is below the limit of detection (100 pg/µl) of Qubit assay as both extraction kits are intended for samples with low bacterial counts. The pre-mixed bacterial pellets at high concentrations with an input of 2 x106 cells for MSA-2002 and 1 x106 cells from MSA-2003 were not compatible with the kits. Among the remaining 3 extraction kits, kit A produced the greatest yield whereas kit B provided the least yield (Kit-A/MSA-2002: 174.25 ± 34.98; Kit-A/MSA-2003: 179.89 ± 30.18; Kit-B/MSA-2002: 27.86 ± 9.35; Kit-B/MSA-2003: 23.14 ± 6.39; Kit-C/MSA-2002: 55.19 ± 10.18; Kit-C/MSA-2003: 35.80 ± 11.41 (Mean ± SD)). Also, kit A produced the greatest yield, whereas kit B provided the least yield. The PCoA 3D visualization of the Weighted Unifrac beta diversity shows that kits A and C cluster closely together while kit B appears as an outlier. The kit A sequencing samples cluster more closely together than both the other kits. The taxonomic profiles of kit B have lower recall when compared to the known mixture profiles indicating that kit B was inefficient at detecting some of the bacteria. Conclusion: Our data demonstrated that the DNA extraction method impacts DNA concentration, purity, and microbial communities detected by next-generation sequencing analysis. Further microbiome analysis performance comparison of using healthy stool samples is underway; also, colorectal cancer patients' samples will be acquired for further explore the clinical utilities. Collectively, our comprehensive qualification approach, including the evaluation of optimal DNA extraction conditions, the inclusion of positive controls, and the implementation of a robust qualified bioinformatics pipeline, assures accurate characterization of the microbiota in a complex matrix for deciphering the deep biology and enabling precision medicine.Keywords: 16S rRNA sequencing, analytical validation, bioinformatics pipeline, metagenomics
Procedia PDF Downloads 170535 A Review on the Mechanism Removal of Pesticides and Heavy Metal from Agricultural Runoff in Treatment Train
Authors: N. A. Ahmad Zubairi, H. Takaijudin, K. W. Yusof
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Pesticides have been used widely over the world in agriculture to protect from pests and reduce crop losses. However, it affects the environment with toxic chemicals. Exceed of toxic constituents in the ecosystem will result in bad side effects. The hydrological cycle is related to the existence of pesticides and heavy metal which it can penetrate through varieties of sources into the soil or water bodies, especially runoff. Therefore, proper mechanisms of pesticide and heavy metal removal should be studied to improve the quality of ecosystem free or reduce from unwanted substances. This paper reviews the use of treatment train and its mechanisms to minimize pesticides and heavy metal from agricultural runoff. Organochlorine (OCL) is a common pesticide that was found in the agricultural runoff. OCL is one of the toxic chemicals that can disturb the ecosystem such as inhibiting plants' growth and harm human health by having symptoms as asthma, active cancer cell, vomit, diarrhea, etc. Thus, this unwanted contaminant gives disadvantages to the environment and needs treatment system. Hence, treatment train by bioretention system is suitable because removal efficiency achieves until 90% of pesticide removal with selected vegetated plant and additive.Keywords: pesticides, heavy metal, agricultural runoff, bioretention, mechanism removal, treatment train
Procedia PDF Downloads 157534 Mechanistic Structural Insights into the UV Induced Apoptosis via Bcl-2 proteins
Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra
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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.Keywords: Bid, Bcl-xl, UVC, apoptosis
Procedia PDF Downloads 127533 Multiple Primary Pulmonary Meningiomas: A Case Report
Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe
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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules
Procedia PDF Downloads 114532 Neutron Contamination in 18 MV Medical Linear Accelerator
Authors: Onur Karaman, A. Gunes Tanir
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Photon radiation therapy used to treat cancer is one of the most important methods. However, photon beam collimator materials in Linear Accelerator (LINAC) head generally contains heavy elements is used and the interaction of bremsstrahlung photon with such heavy nuclei, the neutron can be produced inside the treatment rooms. In radiation therapy, neutron contamination contributes to the risk of secondary malignancies in patients, also physicians working in this field. Since the neutron is more dangerous than photon, it is important to determine neutron dose during radiotherapy treatment. In this study, it is aimed to analyze the effect of field size, distance from axis and depth on the amount of in-field and out-field neutron contamination for ElektaVmat accelerator with 18 MV nominal energy. The photon spectra at the distance of 75, 150, 225, 300 cm from target and on the isocenter of beam were scored for 5x5, 10x10, 20x20, 30x30 and 40x40 cm2 fields. Results demonstrated that the neutron spectra and dose are dependent on field size and distances. Beyond 225 cm of isocenter, the dependence of the neutron dose on field size is minimal. As a result, it is concluded that as the open field increases, neutron dose determined decreases. It is important to remember that when treating with high energy photons, the dose from contamination neutrons must be considered as it is much greater than the photon dose.Keywords: radiotherapy, neutron contamination, linear accelerators, photon
Procedia PDF Downloads 348531 Amniotic Fluid Mesenchymal Stem Cells Selected for Neural Specificity Ameliorates Chemotherapy Induced Hearing Loss and Pain Perception
Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde
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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine
Procedia PDF Downloads 166530 Improving Oxidative Stability of Encapsulated Krill and Black Cumin Oils and its Application in Functional Yogurt
Authors: Tamer El-Messery, Beraat Ozcelik
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This study aimed to produce functional yogurt supplemented with microencapsulated krill oil as a source of omega 3, which is known, to maintain the normal brain function, reduce the risk of cancer, and preventing cardiovascular disease. Krill oil was mixed with black cumin oil (1:1) in order to increase its oxidative stability. β-caroteine (10 mg/100 ml) was used as a standard antioxidant. Maltodextrin (MD) was mixed with whey protein concentrate (WPC) and gum Arabic (GA) at the ratio of 8:2:0.5 ratios and used for microencapsulation of single or mixed oils. The microcapsules were dried by freeze and spray drying in order to maximize encapsulation efficiency and minimize lipid oxidation. The feed emulsions used for particle production were characterized for stability, viscosity and particle size, zeta potential, and oxidative stability. The oxidative stability for mixed krill oil and black cumin oil was the highest. The highest encapsulation efficiency was obtained using spray drying, which also showed the highest oxidative stability. The addition of encapsulated krill and black cumin oils (1:1) powder in yogurt manufacture reduced slightly effects on the development of acidity, textural parameters, and water holding capacity of yogurt as compared to control.Keywords: Krill oil, black cumin oil, micro-encapsulation, oxidative stability, functional yogurt
Procedia PDF Downloads 107529 Ground Water Contamination by Tannery Effluents and Its Impact on Human Health in Peshawar, Pakistan
Authors: Fawad Ali, Muhammad Ateeq, Ikhtiar Khan
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Ground water, a major source of drinking water supply in Peshawar has been severely contaminated by leather tanning industry. Effluents from the tanneries contain high concentration of chromium besides several other chemical species. Release of untreated effluents from the tanning industry has severely damaged surface and ground water, agriculture soil as well as vegetables and crops. Chromium is a well-known carcinogenic and mutagenic agent. Once in the human food chain, it causes multiple problems to the exposed population including various types of cancer, skin dermatitis, and DNA damage. In order to assess the extent of chromium and other heavy metals contamination, water samples were analyzed for heavy metals using Graphite Furnace Atomic Absorption Spectrometer (GFAAS, Analyst 700, Perkin Elmer). Total concentration of chromium was above the permissible limit (0.048 mg/l) in 85% of the groundwater (drinking water) samples. The concentration of cobalt, manganese, cadmium, nickel, lead, zinc and iron was also determined in the ground water, surface water, agriculture soil, and vegetables samples from the affected area.Keywords: heavy metals, soil, groundwater, tannery effluents, food chain
Procedia PDF Downloads 346528 Simultaneous Removal of Arsenic and Toxic Metals from Contaminated Soil: a Pilot-Scale Demonstration
Authors: Juan Francisco Morales Arteaga, Simon Gluhar, Anela Kaurin, Domen Lestan
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Contaminated soils are recognized as one of the most pressing global environmental problems. As is one of the most hazardous elements: chronic exposure to arsenic has devastating effects on health, cardiovascular diseases, cancer, and eventually death. Pb, Zn and Cd are very highly toxic metals that affect almost every organ in the body. With this in mind, new technologies for soil remediation processes are urgently needed. Calcareous artificially contaminated soil containing 231 mg kg-1 As and historically contaminated with Pb, Zn and Cd was washed with a 1:1.5 solid-liquid ratio of 90 mM EDTA, 100 mM oxalic acid, and 50 mM sodium dithionite to remove 59, 75, 29, and 53% of As, Pb, Zn, and Cd, respectively. To reduce emissions of residual EDTA and chelated metals from the remediated soil, zero valent iron (ZVI) was added (1% w/w) to the slurry of the washed soil immediately prior to rinsing. Experimental controls were conducted without the addition of ZVI after remediation. The use of ZVI reduced metal leachability and minimized toxic emissions 21 days after remediation. After this time, NH4NO3 extraction was performed to determine the mobility of toxic elements in the soil. In addition, Unified Human BioaccessibilityMethod (UBM) was performed to quantify the bioaccessibility levels of metals in stimulated human gastric and gastrointestinal phases.Keywords: soil remediation, soil science, soil washing, toxic metals removal
Procedia PDF Downloads 175527 Serological Assay and Genotyping of Hepatitis C Virus in Infected Patients in Zanjan Province
Authors: Abdolreza Esmaeilzadeh, Maryam Erfanmanesh, Sousan Ghasemi, Farzaneh Mohammadi
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Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment.Keywords: anti-HCV antibody, Hepatitis C Virus (HCV), genotype, RT-PCR, AS-PCR
Procedia PDF Downloads 489526 Curcumin and Methotrexate Loaded Montmollilite Clay for Sustained Oral Drug Delivery Application
Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das
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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity
Procedia PDF Downloads 515525 Impact of Land-Use and Climate Change on the Population Structure and Distribution Range of the Rare and Endangered Dracaena ombet and Dobera glabra in Northern Ethiopia
Authors: Emiru Birhane, Tesfay Gidey, Haftu Abrha, Abrha Brhan, Amanuel Zenebe, Girmay Gebresamuel, Florent Noulèkoun
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Dracaena ombet and Dobera glabra are two of the most rare and endangered tree species in dryland areas. Unfortunately, their sustainability is being compromised by different anthropogenic and natural factors. However, the impacts of ongoing land use and climate change on the population structure and distribution of the species are less explored. This study was carried out in the grazing lands and hillside areas of the Desa'a dry Afromontane forest, northern Ethiopia, to characterize the population structure of the species and predict the impact of climate change on their potential distributions. In each land-use type, abundance, diameter at breast height, and height of the trees were collected using 70 sampling plots distributed over seven transects spaced one km apart. The geographic coordinates of each individual tree were also recorded. The results showed that the species populations were characterized by low abundance and unstable population structure. The latter was evinced by a lack of seedlings and mature trees. The study also revealed that the total abundance and dendrometric traits of the trees were significantly different between the two land uses. The hillside areas had a denser abundance of bigger and taller trees than the grazing lands. Climate change predictions using the MaxEnt model highlighted that future temperature increases coupled with reduced precipitation would lead to significant reductions in the suitable habitats of the species in northern Ethiopia. The species' suitable habitats were predicted to decline by 48–83% for D. ombet and 35–87% for D. glabra. Hence, to sustain the species populations, different strategies should be adopted, namely the introduction of alternative livelihoods (e.g., gathering NTFP) to reduce the overexploitation of the species for subsistence income and the protection of the current habitats that will remain suitable in the future using community-based exclosures. Additionally, the preservation of the species' seeds in gene banks is crucial to ensure their long-term conservation.Keywords: grazing lands, hillside areas, land-use change, MaxEnt, range limitation, rare and endangered tree species
Procedia PDF Downloads 96524 Microdosimetry in Biological Cells: A Monte Carlo Method
Authors: Hamidreza Jabal Ameli, Anahita Movahedi
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Purpose: In radionuclide therapy, radioactive atoms are coupled to monoclonal antibodies (mAbs) for treating cancer tumor while limiting radiation to healthy tissues. We know that tumoral and normal tissues are not equally sensitive to radiation. In fact, biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells should be taken account. For this reason, in this paper, we want to calculate biological effect dose (BED) inside tumoral area and healthy cells around tumors. Methods: In this study, deposited doses of a radionuclide, gold-198, inside cells lattice and surrounding healthy tissues were calculated with Monte Carlo method. The elemental compositions and density of malignant and healthy tissues were obtained from ICRU Report 44. For reaching to real condition of oxygen effects, the necrosis and hypoxia area inside tumors has been assessed. Results: With regard to linear-quadratic expression which was defined in Monte Carlo, results showed that a large amount of BED is deposited in the well-oxygenated part of the hypoxia area compared to necrosis area. Moreover, there is a significant difference between the curves of absorbed dose with BED and without BED.Keywords: biological dose, monte carlo, hypoxia, radionuclide therapy
Procedia PDF Downloads 486523 Optimization of the Self-Recognition Direct Digital Radiology Technology by Applying the Density Detector Sensors
Authors: M. Dabirinezhad, M. Bayat Pour, A. Dabirinejad
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In 2020, the technology was introduced to solve some of the deficiencies of direct digital radiology. SDDR is an invention that is capable of capturing dental images without human intervention, and it was invented by the authors of this paper. Adjusting the radiology wave dose is a part of the dentists, radiologists, and dental nurses’ tasks during the radiology photography process. In this paper, an improvement will be added to enable SDDR to set the suitable radiology wave dose according to the density and age of the patients automatically. The separate sensors will be included in the sensors’ package to use the ultrasonic wave to detect the density of the teeth and change the wave dose. It facilitates the process of dental photography in terms of time and enhances the accuracy of choosing the correct wave dose for each patient separately. Since the radiology waves are well known to trigger off other diseases such as cancer, choosing the most suitable wave dose can be helpful to decrease the side effect of that for human health. In other words, it decreases the exposure time for the patients. On the other hand, due to saving time, less energy will be consumed, and saving energy can be beneficial to decrease the environmental impact as well.Keywords: dental direct digital imaging, environmental impacts, SDDR technology, wave dose
Procedia PDF Downloads 194522 Stability Analysis of Tumor-Immune Fractional Order Model
Authors: Sadia Arshad, Yifa Tang, Dumitru Baleanu
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A fractional order mathematical model is proposed that incorporate CD8+ cells, natural killer cells, cytokines and tumor cells. The tumor cells growth in the absence of an immune response is modeled by logistic law as it was the simplest form for which predictions also agreed with the experimental data. Natural Killer Cells are our first line of defense. NK cells directly kill tumor cells through several mechanisms, including the release of cytoplasmic granules containing perforin and granzyme, expression of tumor necrosis factor (TNF) family members. The effect of the NK cells on the tumor cell population is expressed with the product term. Rational form is used to describe interaction between CD8+ cells and tumor cells. A number of cytokines are produced by NKs, including tumor necrosis factor TNF, IFN, and interleukin (IL-10). Source term for cytokines is modeled by Michaelis-Menten form to indicate the saturated effects of the immune response. Stability of the equilibrium points is discussed for biologically significant values of bifurcation parameters. We studied the treatment of fractional order system by investigating analytical conditions of tumor eradication. Numerical simulations are presented to illustrate the analytical results.Keywords: cancer model, fractional calculus, numerical simulations, stability analysis
Procedia PDF Downloads 315521 Genetic Improvement Potential for Wood Production in Melaleuca cajuputi
Authors: Hong Nguyen Thi Hai, Ryota Konda, Dat Kieu Tuan, Cao Tran Thanh, Khang Phung Van, Hau Tran Tin, Harry Wu
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Melaleuca cajuputi is a moderately fast-growing species and considered as a multi-purpose tree as it provides fuelwood, piles and frame poles in construction, leaf essential oil and honey. It occurs in Australia, Papua New Guinea, and South-East Asia. M. cajuputi plantation can be harvested on 6-7 year rotations for wood products. Its timber can also be used for pulp and paper, fiber and particle board, producing quality charcoal and potentially sawn timber. However, most reported M. cajuputi breeding programs have been focused on oil production rather than wood production. In this study, breeding program of M. cajuputi aimed to improve wood production was examined by estimating genetic parameters for growth (tree height, diameter at breast height (DBH), and volume), stem form, stiffness (modulus of elasticity (MOE)), bark thickness and bark ratio in a half-sib family progeny trial including 80 families in the Mekong Delta of Vietnam. MOE is one of the key wood properties of interest to the wood industry. Non-destructive wood stiffness was measured indirectly by acoustic velocity using FAKOPP Microsecond Timer and especially unaffected by bark mass. Narrow-sense heritability for the seven traits ranged from 0.13 to 0.27 at age 7 years. MOE and stem form had positive genetic correlations with growth while the negative correlation between bark ratio and growth was also favorable. Breeding for simultaneous improvement of multiple traits, faster growth with higher MOE and reduction of bark ratio should be possible in M. cajuputi. Index selection based on volume and MOE showed genetic gains of 31 % in volume, 6 % in MOE and 13 % in stem form. In addition, heritability and age-age genetic correlations for growth traits increased with time and optimal early selection age for growth of M. cajuputi based on DBH alone was 4 years. Selected thinning resulted in an increase of heritability due to considerable reduction of phenotypic variation but little effect on genetic variation.Keywords: acoustic velocity, age-age correlation, bark thickness, heritability, Melaleuca cajuputi, stiffness, thinning effect
Procedia PDF Downloads 182520 An Investigation of Anticancer Fluorinated Aza-Heterocycles
Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev
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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis
Procedia PDF Downloads 339519 Heterocyclic Ring Extension of Estrone: Synthesis and Cytotoxicity of Fused Pyrin, Pyrimidine and Thiazole Derivatives
Authors: Rafat M. Mohareb
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Several D-ring alkylated estrone analogues display exceptionally high affinity for estrogen receptors. In particular, compounds in which an E-ring is formed are known to be involved in the inhibition of steroidogenic enzymes. Such compounds also have an effect on steroid dehydrogenase activity and the ability to inhibit the detrimental action of the steroid sulfatase enzyme. Generally, E-ring extended steroids have been accessed by modification of the C17-ketone in the D-ring by either arylimine or oximino formation, addition of a carbon nucleophile or hydrazone formation. Other approaches have included ketone reduction, silyl enol ether formation or ring-closing metathesis (giving five- or six-membered E-rings). Chemical modification of the steroid D-ring provides a way to alter the functional groups, sizes and stereochemistry of the D-ring, and numerous structure-activity relationships have been established by such synthetic alterations. Steroids bearing heterocycles fused to the D-ring of the steroid nucleus have been of pharmaceutical interest. In the present paper, we report on the efficient synthesis of estrone possessing pyran, pyrimidine and thiazole ring systems. This study focused on the synthesis and biochemical evaluation of newly synthesized heterocyclic compounds which were then subjected through inhibitory evaluations towards human cancer and normal cell lines.Keywords: estrone, heterocyclization, cytotoxicity, biomedicine
Procedia PDF Downloads 295518 Developing Allometric Equations for More Accurate Aboveground Biomass and Carbon Estimation in Secondary Evergreen Forests, Thailand
Authors: Titinan Pothong, Prasit Wangpakapattanawong, Stephen Elliott
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Shifting cultivation is an indigenous agricultural practice among upland people and has long been one of the major land-use systems in Southeast Asia. As a result, fallows and secondary forests have come to cover a large part of the region. However, they are increasingly being replaced by monocultures, such as corn cultivation. This is believed to be a main driver of deforestation and forest degradation, and one of the reasons behind the recurring winter smog crisis in Thailand and around Southeast Asia. Accurate biomass estimation of trees is important to quantify valuable carbon stocks and changes to these stocks in case of land use change. However, presently, Thailand lacks proper tools and optimal equations to quantify its carbon stocks, especially for secondary evergreen forests, including fallow areas after shifting cultivation and smaller trees with a diameter at breast height (DBH) of less than 5 cm. Developing new allometric equations to estimate biomass is urgently needed to accurately estimate and manage carbon storage in tropical secondary forests. This study established new equations using a destructive method at three study sites: approximately 50-year-old secondary forest, 4-year-old fallow, and 7-year-old fallow. Tree biomass was collected by harvesting 136 individual trees (including coppiced trees) from 23 species, with a DBH ranging from 1 to 31 cm. Oven-dried samples were sent for carbon analysis. Wood density was calculated from disk samples and samples collected with an increment borer from 79 species, including 35 species currently missing from the Global Wood Densities database. Several models were developed, showing that aboveground biomass (AGB) was strongly related to DBH, height (H), and wood density (WD). Including WD in the model was found to improve the accuracy of the AGB estimation. This study provides insights for reforestation management, and can be used to prepare baseline data for Thailand’s carbon stocks for the REDD+ and other carbon trading schemes. These may provide monetary incentives to stop illegal logging and deforestation for monoculture.Keywords: aboveground biomass, allometric equation, carbon stock, secondary forest
Procedia PDF Downloads 284517 Preventive Impact of Regional Analgesia on Chronic Neuropathic Pain After General Surgery
Authors: Beloulou Mohamed Lamine, Fedili Benamar, Meliani Walid, Chaid Dalila, Lamara Abdelhak
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Introduction: Post-surgical chronic pain (PSCP) is a pathological condition with a rather complex etiopathogenesis that extensively involves sensitization processes and neuronal damage. The neuropathic component of these pains is almost always present, with variable expression depending on the type of surgery. Objective: To assess the presumed beneficial effect of Regional Anesthesia-Analgesia Techniques (RAAT) on the development of post-surgical chronic neuropathic pain (PSCNP) in various surgical procedures. Patients and Methods: A comparative study involving 510 patients distributed across five surgical models (mastectomy, thoracotomy, hernioplasty, cholecystectomy, and major abdominal-pelvic surgery) and randomized into two groups: Group A (240) receiving conventional postoperative analgesia and Group B (270) receiving balanced analgesia, including the implementation of a Regional Anesthesia-Analgesia Technique (RAAT). These patients were longitudinally followed over a 6-month period, with postsurgical chronic neuropathic pain (PSCNP) defined by a Neuropathic Pain Score DN2≥ 3. Comparative measurements through univariate and multivariable analyses were performed to identify associations between the development of PSCNP and certain predictive factors, including the presumed preventive impact (protective effect) of RAAT. Results: At the 6th month post-surgery, 419 patients were analyzed (Group A= 196 and Group B= 223). The incidence of PSCNP was 32.2% (n=135). Among these patients with chronic pain, the prevalence of neuropathic pain was 37.8% (95% CI: [29.6; 46.5]), with n=51/135. It was significantly lower in Group B compared to Group A, with respective percentages of 31.4% vs. 48.8% (p-value = 0.035). The most significant differences were observed in breast and thoracopulmonary surgeries. In a multiple regression analysis, two predictors of PSCNP were identified: the presence of preoperative pain at the surgical site as a risk factor (OR: 3.198; 95% CI [1.326; 7.714]) and RAAT as a protective factor (OR: 0.408; 95% CI [0.173; 0.961]). Conclusion: The neuropathic component of PSCNP can be observed in different types of surgeries. Regional analgesia included in a multimodal approach to postoperative pain management has proven to be effective for acute pain and seems to have a preventive impact on the development of PSCNP and its neuropathic nature, particularly in surgeries that are more prone to chronicization.Keywords: post-surgical chronic pain, post-surgical chronic neuropathic pain, regional anesthesia-analgesia techniques, neuropathic pain score DN2, preventive impact
Procedia PDF Downloads 78516 Anti-Obesity Effect of Cordyceps militaris Fermented Black Rice
Authors: Chih-Hung Liang, Jung-Jung Chen, Shen-Shih Chiang
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Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health, which are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Cordyceps militaris (CM) is a well-known traditional medicine in Asian countries and a rich source of biologically active components. Black rice (Oryza sativa L.) is a special cultivar of rice that contains rich anthocyanins and regarded as a health-promoting food in China and other Eastern. The aim of this study was to investigate the anti-obesity effect of Cordyceps militaris fermented black rice (CB) on HFD-induced BALB/c mice model. The results indicated that administration of low and high dosage of CB powder significantly reduced the body weights (7.38% and 7.78%), body fat ratio (2.37% and 2.78%), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels compared to the HF group (p<0.05). Histopathological analysis showed that the score of fatty liver in HF group (5.0) was significantly higher than CB groups (2.1 and 3.6) (p<0.05). In conclusion, Cordyceps militaris fermented black rice can reduce the body weight via inhibition of the fat accumulation in liver and body and possess the anti-obesity potency.Keywords: Cordyceps militaris, black rice, obesity, HFD-induced mice
Procedia PDF Downloads 310515 Prevalence of Adverse Events in Children and Adolescents on Antiretroviral Therapy: Examining the Pediatric Cohort in the Eastern Cape
Authors: Shannon Glaspy, Gerald Boon, Jack Lambert
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Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.Keywords: ARV, adverse events, HAART, pediatric
Procedia PDF Downloads 197514 Light-Emitting Diode Assisted Synthesis of Ag@Fe3O4 Nanoparticles and Their Application in Magnetic and Photothermal Hyperthermia Therapy
Authors: Pei-Wen Lin, Ta-I Yang
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Cancer has been one of the leading causes of human death for centuries. Considerable effort has been devoted to developing new treatments to reduce and control cancers. Magnetic particle hyperthermia and near-infrared photothermal therapy are the promising strategies to treat cancers due to its effectiveness with only mild side effects. This study focused on synthesizing magnetic Ag@Fe3O4 nanoparticles applicable for both of magnetic hyperthermia and near-infrared photothermal therapy. The hydrophilic poly(diallyldimethylammonium chloride) polymer was utilized to prepare superparamagnetic Fe3O4 clusters and to promote silver nanoparticles grown on Fe3O4 surfaces, obtaining Ag@Fe3O4 nanoparticles. The morphology (shape and dimension) of Ag nanoparticles was subsequently tailored using commercial LED lights. Therefore, the resulting Ag@Fe3O4 nanoparticles can absorb specific wavelength of light ranging from 400 nm to 800 nm by adjusting the wavelength of LED lights and the free silver ions in reaction solution. Heating performance tests confirmed that the synthesized Ag@Fe3O4 nanoparticles show appreciable heating capability for both of magnetic particle hyperthermia and near-infrared photothermal therapy. The findings in this study could provide new ideas to design functional materials to treat cancers.Keywords: light-emitting diode assisted synthesis, magnetic particles, photothermal materials, hyperthermia
Procedia PDF Downloads 284513 Trends of Cutaneous Melanoma in New Zealand: 2010 to 2020
Authors: Jack S. Pullman, Daniel Wen, Avinash Sharma, Bert Van Der Werf, Richard Martin
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Background: New Zealand (NZ) melanoma incidence rates are amongst the highest in the world. Previous studies investigating the incidence of melanoma in NZ were performed for the periods 1995 – 1999 and 2000 – 2004 and suggested increasing melanoma incidence rates. Aim: The aim of the study is to provide an up-to-date review of trends in cutaneous melanoma in NZ from the New Zealand Cancer Registry (NZCR) 2010 – 2020. Methods: De-identified data were obtained from the NZCR, and relevant demographic and histopathologic information was extracted. Statistical analyses were conducted to calculate age-standardized incidence rates for invasive melanoma (IM) and melanoma in situ (MIS). Secondary results included Breslow thickness and melanoma subtype analysis. Results: There was a decline in the IM age-standardized incidence rate from 30.4 to 23.9 per 100,000 person-years between 2010 to 2020, alongside an increase in MIS incidence rate from 37.1 to 50.3 per 100,000 person-years. Men had a statistically significant higher IM incidence rate (p <0.001) and Breslow thickness (p <0.001) compared with women. Increased age was associated with a higher incidence of IM, presentation with melanoma of greater Breslow thickness and more advanced T stage. Conclusion: The incidence of IM in NZ has decreased in the last decade and was associated with an increase in MIS incidence over the same period. This can be explained due to earlier detection, dermoscopy, the maturity of prevention campaigns and/or a change in skin protection behavior.Keywords: melanoma, incidence, epidemiology, New Zealand
Procedia PDF Downloads 64512 In-Vivo Association of Multivalent 11 Zinc Fingers Transcriptional Factors CTCF and Boris to YB-1 in Multiforme Glioma-RGBM Cell Line
Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun
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CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine
Procedia PDF Downloads 266511 Sequence Analysis of the Effect of HPV-16 E1 Variation on Cervical Carcinogenesis
Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol
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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1
Procedia PDF Downloads 236510 Differential Infection of Primary Human B-Cells and EBV Positive B-Lymphoma Cell Lines by Recombinant AAV Serotypes
Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping
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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.Keywords: AAV, gene therapy, lymphoma, malignancy, tropism
Procedia PDF Downloads 120509 The Differences of Vascular Endothelial Growth Factor Levels in Serum to Determine Follicular Adenoma and Follicular Carcinoma of Thyroid
Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto
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Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF
Procedia PDF Downloads 142508 Patients' Perceptions of Receiving a Diagnosis of a Haematological Malignancy, following the SPIKES Protocol
Authors: Lauren Dixon, David Galvani
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Objective: Sharing devastating news with patients is often considered the most difficult task of doctors. This study aimed to explore patients’ perceptions of receiving bad news including which features improve the experience and which areas need refining. Methods: A questionnaire was written based on the steps of the SPIKES model for breaking bad news. 20 patients receiving treatment for a haematological malignancy completed the questionnaire. Results: Overall, the results are promising as most patients praised their consultation. ‘Poor’ was more commonly rated by women and participants aged 45-64. The main differences between the ‘excellent’ and ‘poor’ consultations include the doctor’s sensitivity and checking the patients’ understanding. Only 35% of patients were asked their existing knowledge and 85% of consultations failed to discuss the impact of the diagnosis on daily life. Conclusion: This study agreed with the consensus of existing literature. The commended aspects include consultation set-up and information given. Areas patients felt needed improvement include doctors determining the patient’s existing knowledge and exploring how the diagnosis will affect the patient’s life. With a poorer prognosis, doctors should work on conveying appropriate hope. The study was limited by a small sample size and potential recall bias.Keywords: cancer, diagnosis, haematology, patients
Procedia PDF Downloads 313