Search results for: cancer drugs
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 381

Search results for: cancer drugs

291 ‘Memory Mate’ as Boundary Object in Cancer Treatment for Patients with Dementia

Authors: Rachel Hurdley, Jane Hopkinson

Abstract:

This article is based on observation of a cross-disciplinary, cross-institutional team that worked on an intervention called ‘Memory Mate’ for use in a UK Cancer Centre. This aimed to improve treatment outcomes for patients who had comorbid dementia or other memory impairment. Comorbid patients present ambiguous, spoiled identities, problematising the boundaries of health specialisms and frames of understanding. Memory Mate is theorised as a boundary object facilitating service transformation by changing relations between oncology and mental health care practice. It crosses the boundaries between oncology and mental health. Its introduction signifies an important step in reconfiguring relations between the specialisms. As a boundary object, it contains parallel, even contesting worlds, with potential to enable an eventual synthesis of the double stigma of cancer and dementia. Memory Mate comprises physical things, such as an animation, but its principal value is in the interaction it initiates across disciplines and services. It supports evolution of practices to address a newly emergent challenge for health service provision, namely the cancer patient with comorbid dementia/cognitive impairment. Getting clinicians from different disciplines working together on a practical solution generates a dialogue that can shift professional identity and change the culture of practice.

Keywords: Boundary object, cancer, dementia, interdisciplinary teams.

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290 Computer Modeling of Drug Distribution after Intravitreal Administration

Authors: N. Haghjou, M. J. Abdekhodaie, Y. L. Cheng, M. Saadatmand

Abstract:

Intravitreal injection (IVI) is the most common treatment for eye posterior segment diseases such as endopthalmitis, retinitis, age-related macular degeneration, diabetic retinopathy, uveitis, and retinal detachment. Most of the drugs used to treat vitreoretinal diseases, have a narrow concentration range in which they are effective, and may be toxic at higher concentrations. Therefore, it is critical to know the drug distribution within the eye following intravitreal injection. Having knowledge of drug distribution, ophthalmologists can decide on drug injection frequency while minimizing damage to tissues. The goal of this study was to develop a computer model to predict intraocular concentrations and pharmacokinetics of intravitreally injected drugs. A finite volume model was created to predict distribution of two drugs with different physiochemical properties in the rabbit eye. The model parameters were obtained from literature review. To validate this numeric model, the in vivo data of spatial concentration profile from the lens to the retina were compared with the numeric data. The difference was less than 5% between the numerical and experimental data. This validation provides strong support for the numerical methodology and associated assumptions of the current study.

Keywords: Posterior segment, Intravitreal injection (IVI), Pharmacokinetic, Modelling, Finite volume method.

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289 Antibody-Conjugated Nontoxic Arginine-Doped Fe3O4 Nanoparticles for Magnetic Circulating Tumor Cells Separation

Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

Abstract:

Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe3O4 nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: Tumor tissue, antibody, magnetic nanoparticle, CTCs capturing.

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288 Identification of Complex Sense-antisense Gene's Module on 17q11.2 Associated with Breast Cancer Aggressiveness and Patient's Survival

Authors: O. Grinchuk, E. Motakis, V. Kuznetsov

Abstract:

Sense-antisense gene pair (SAGP) is a pair of two oppositely transcribed genes sharing a common region on a chromosome. In the mammalian genomes, SAGPs can be organized in more complex sense-antisense gene architectures (CSAGA) in which at least one gene could share loci with two or more antisense partners. Many dozens of CSAGAs can be found in the human genome. However, CSAGAs have not been systematically identified and characterized in context of their role in human diseases including cancers. In this work we characterize the structural-functional properties of a cluster of 5 genes –TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199, termed TNFAIP1 / POLDIP2 module. This cluster is organized as CSAGA in cytoband 17q11.2. Affymetrix U133A&B expression data of two large cohorts (410 atients, in total) of breast cancer patients and patient survival data were used. For the both studied cohorts, we demonstrate (i) strong and reproducible transcriptional co-regulatory patterns of genes of TNFAIP1/POLDIP2 module in breast cancer cell subtypes and (ii) significant associations of TNFAIP1/POLDIP2 CSAGA with amplification of the CSAGA region in breast cancer, (ii) cancer aggressiveness (e.g. genetic grades) and (iv) disease free patient-s survival. Moreover, gene pairs of this module demonstrate strong synergetic effect in the prognosis of time of breast cancer relapse. We suggest that TNFAIP1/ POLDIP2 cluster can be considered as a novel type of structural-functional gene modules in the human genome.

Keywords: Sense-antisense gene pair, complex genome architecture, TMEM97, IFT20, TNFAIP1, POLDIP2, TMEM199, 17q11.2, breast cancer, transcription regulation, survival analysis, prognosis.

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287 Feature Subset Selection approach based on Maximizing Margin of Support Vector Classifier

Authors: Khin May Win, Nan Sai Moon Kham

Abstract:

Identification of cancer genes that might anticipate the clinical behaviors from different types of cancer disease is challenging due to the huge number of genes and small number of patients samples. The new method is being proposed based on supervised learning of classification like support vector machines (SVMs).A new solution is described by the introduction of the Maximized Margin (MM) in the subset criterion, which permits to get near the least generalization error rate. In class prediction problem, gene selection is essential to improve the accuracy and to identify genes for cancer disease. The performance of the new method was evaluated with real-world data experiment. It can give the better accuracy for classification.

Keywords: Microarray data, feature selection, recursive featureelimination, support vector machines.

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286 Intellectual Property Rights and Health Rights: A Feasible Reform Proposal to Facilitate Access to Drugs in Developing Countries

Authors: M. G. Cattaneo

Abstract:

The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: Global health, global justice, patent law reform, access to drugs.

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285 Awareness for Air Pollution Impacts on Lung Cancer in Southern California: A Pilot Study for Designed Smartphone Application

Authors: M. Mohammed Raoof, A. Enkhtaivan, H. Aljuaid

Abstract:

This study follows the design science research methodology to design and implement a smartphone application artifact. The developed artifact was evaluated through three phases. The System Usability Scale (SUS) metric was used for the evaluation. The designed artifact aims to spread awareness about reducing air pollution, decreasing lung cancer development, and checking the air quality status in Southern California Counties. Participants have been drawn for a pilot study to facilitate awareness of air pollution. The study found that smartphone applications have a beneficial effect on the study’s aims.

Keywords: Air pollution, design science research, indoor air pollution, lung cancer, outdoor air pollution, smartphone application.

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284 Automatic Detection and Classification of Microcalcification, Mass, Architectural Distortion and Bilateral Asymmetry in Digital Mammogram

Authors: S. Shanthi, V. Muralibhaskaran

Abstract:

Mammography has been one of the most reliable methods for early detection of breast cancer. There are different lesions which are breast cancer characteristic such as microcalcifications, masses, architectural distortions and bilateral asymmetry. One of the major challenges of analysing digital mammogram is how to extract efficient features from it for accurate cancer classification. In this paper we proposed a hybrid feature extraction method to detect and classify all four signs of breast cancer. The proposed method is based on multiscale surrounding region dependence method, Gabor filters, multi fractal analysis, directional and morphological analysis. The extracted features are input to self adaptive resource allocation network (SRAN) classifier for classification. The validity of our approach is extensively demonstrated using the two benchmark data sets Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammograph (DDSM) and the results have been proved to be progressive.

Keywords: Feature extraction, fractal analysis, Gabor filters, multiscale surrounding region dependence method, SRAN.

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283 Chemotherapy Safety Protocol for Oncology Nurses: It's Effect on Their Protective Measures Practices

Authors: Magda M. Mohsen, Manal E. Fareed

Abstract:

Background: Widespread use of chemotherapeutic drugs in the treatment of cancer has lead to higher health hazards among employee who handle and administer such drugs, so nurses should know how to protect themselves, their patients and their work environment against toxic effects of chemotherapy. Aim of this study was carried out to examine the effect of chemotherapy safety protocol for oncology nurses on their protective measure practices. Design: A quasi experimental research design was utilized. Setting: The study was carried out in oncology department of Menoufia university hospital and Tanta oncology treatment center. Sample: A convenience sample of forty five nurses in Tanta oncology treatment center and eighteen nurses in Menoufiya oncology department. Tools: 1. an interviewing questionnaire that covering sociodemographic data, assessment of unit and nurses' knowledge about chemotherapy. II: Obeservational check list to assess nurses' actual practices of handling and adminestration of chemotherapy. A base line data were assessed before implementing Chemotherapy Safety protocol, then Chemotherapy Safety protocol was implemented, and after 2 monthes they were assessed again. Results: reveled that 88.9% of study group I and 55.6% of study group II improved to good total knowledge scores after educating on the safety protocol, also 95.6% of study group I and 88.9% of study group II had good total practice score after educating on the safety protocol. Moreover less than half of group I (44.4%) reported that heavy workload is the most barriers for them, while the majority of group II (94.4%) had many barriers for adhering to the safety protocol such as they didn’t know the protocol, the heavy work load and inadequate equipment. Conclusions: Safety protocol for Oncology Nurses seemed to have positive effect on improving nurses' knowledge and practice. Recommendation: chemotherapy safety protocol should be instituted for all oncology nurses who are working in any oncology unit and/ or center to enhance compliance, and this protocol should be done at frequent intervals.

Keywords: Chemotherapy Safety protocol, Effect, protective measure practice.

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282 Gene Expression Signature for Classification of Metastasis Positive and Negative Oral Cancer in Homosapiens

Authors: A. Shukla, A. Tarsauliya, R. Tiwari, S. Sharma

Abstract:

Cancer classification to their corresponding cohorts has been key area of research in bioinformatics aiming better prognosis of the disease. High dimensionality of gene data has been makes it a complex task and requires significance data identification technique in order to reducing the dimensionality and identification of significant information. In this paper, we have proposed a novel approach for classification of oral cancer into metastasis positive and negative patients. We have used significance analysis of microarrays (SAM) for identifying significant genes which constitutes gene signature. 3 different gene signatures were identified using SAM from 3 different combination of training datasets and their classification accuracy was calculated on corresponding testing datasets using k-Nearest Neighbour (kNN), Fuzzy C-Means Clustering (FCM), Support Vector Machine (SVM) and Backpropagation Neural Network (BPNN). A final gene signature of only 9 genes was obtained from above 3 individual gene signatures. 9 gene signature-s classification capability was compared using same classifiers on same testing datasets. Results obtained from experimentation shows that 9 gene signature classified all samples in testing dataset accurately while individual genes could not classify all accurately.

Keywords: Cancer, Gene Signature, SAM, Classification.

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281 Evolutionary of Prostate Cancer Stem Cells in Prostate Duct

Authors: Zachariah Sinkala

Abstract:

A systems approach model for prostate cancer in prostate duct, as a sub-system of the organism is developed. It is accomplished in two steps. First this research work starts with a nonlinear system of coupled Fokker-Plank equations which models continuous process of the system like motion of cells. Then extended to PDEs that include discontinuous processes like cell mutations, proliferation and deaths. The discontinuous processes is modeled by using intensity poisson processes. The model incorporates the features of the prostate duct. The system of PDEs spatial coordinate is along the proximal distal axis. Its parameters depend on features of the prostate duct. The movement of cells is biased towards distal region and mutations of prostate cancer cells is localized in the proximal region. Numerical solutions of the full system of equations are provided, and are exhibit traveling wave fronts phenomena. This motivates the use of the standard transformation to derive a canonically related system of ODEs for traveling wave solutions. The results obtained show persistence of prostate cancer by showing that the non-negative cone for the traveling wave system is time invariant. The traveling waves have a unique global attractor is proved also. Biologically, the global attractor verifies that evolution of prostate cancer stem cells exhibit the avascular tumor growth. These numerical solutions show that altering prostate stem cell movement or mutation of prostate cancer cells lead to avascular tumor. Conclusion with comments on clinical implications of the model is discussed.

Keywords: Fokker-Plank equations, global attractor, stem cell.

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280 Evolution of Cord Absorbed Dose during of Larynx Cancer Radiotherapy, with 3D Treatment Planning and Tissue Equivalent Phantom

Authors: Mohammad Hassan Heidari, Amir Hossein Goodarzi, Majid Azarniush

Abstract:

Radiation doses to tissues and organs were measured using the anthropomorphic phantom as an equivalent to the human body. When high-energy X-rays are externally applied to treat laryngeal cancer, the absorbed dose at the laryngeal lumen is lower than given dose because of air space, which it should pass through, before reaching the lesion. Specially, in case of high-energy X-rays, the loss of dose is considerable. Three-dimensional absorbed dose distributions have been computed for high-energy photon radiation therapy of laryngeal and hypopharyngeal cancers, using a coaxial pair of opposing lateral beams in fixed positions. Treatment plans obtained under various conditions of irradiation.

Keywords: 3D Treatment Planning, anthropomorphic phantom, larynx cancer, radiotherapy.

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279 Preparation, Characterisation, and Measurement of the in vitro Cytotoxicity of Mesoporous Silica Nanoparticles Loaded with Cytotoxic Pt(II) Oxadiazoline Complexes

Authors: G. Wagner, R. Herrmann

Abstract:

Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: Cytotoxicity, mesoporous silica, nanoparticles platinum compounds.

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278 Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells

Authors: Amaneh Javid, Shahin Ahmadian, Ali A. Saboury, Saeed Rezaei-Zarchi

Abstract:

This study determines the effect of naked and heparinbased super-paramagnetic iron oxide nanoparticles on the human cancer cell lines of A2780. Doxorubicin was used as the anticancer drug, entrapped in the SPIO-NPs. This study aimed to decorate nanoparticles with heparin, a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. The nanoparticles containing the anticancer drug DOX were prepared by a solvent evaporation and emulsification cross-linking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of DOX from the SPIO-NPs was successful. Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell toxicity than the individual HP and confocal microscopy analysis confirmed excellent cellular uptake efficiency. These results indicate that HP based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Keywords: Heparin, A2780 cells, ovarian cancer, nanoparticles, doxorubicin.

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277 Comparative in silico and in vitro Study of N-(1- Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent

Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

Abstract:

Doxorubicin, also known as Adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemia, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, antiinflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl) benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2 μM.

Keywords: Anticancer, Auto Dock, Doxorubicin, Sulfonamide.

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276 Non-Melanoma Skin Cancer in Ha’il Region in the Kingdom of Saudi Arabia: A Clinicopathological Study

Authors: Laila Seada, Nouf Al Gharbi, Shaimaa Dawa

Abstract:

Although skin cancers are prevalent worldwide, it is uncommon in Ha’il region in the Kingdom of Saudi Arabia, mostly non-melanoma sub-type. During a 4-year period from 2014 to 2017, out of a total of 120 cases of skin lesions, 29 non-melanoma cancers were retrieved from histopathology files obtained from King Khalid Hospital. As part of the study, all cases of skin cancer diagnosed during 2014 -2017 have been revised and the clinicopathological data recorded. The results show that Basal cell carcinoma (BCC) was the most common neoplasm (36%), followed by cutaneous lymphomas (mostly mycosis fungoides 25%), squamous cell carcinoma (SCC) (21%) and dermatofibrosarcoma protuberans (DFSP) (11%). Only one case of metastatic carcinoma was recorded. BCC nodular type was the most prevalent, with a mean age 57.6 years and mean size 2.73 cm. SCC was mostly grade 2, with mean size 1.9 cm and an older mean age of 72.3 cm. Increased size of lesion positively correlated with older age (p = 0.001). Non-melanoma skin cancer in Ha’il region is not frequently encountered. BCC is the most frequent followed by cutaneous T-cell lymphomas and SCC. The findings in this study were in accordance with other parts of, but much lower than other parts of the world.

Keywords: Non melanoma skin cancer, Hail Region, histopathology, BCC.

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275 Evaluation of Systemic Immune-Inflammation Index in Obese Children

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: Children, c- reactive protein, systemic immune-inflammation index, obesity.

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274 Computer Aided Drug Design and Studies of Antiviral Drug against H3N2 Influenza Virus

Authors: Aditi Shukla, Ambarish S. Vidyarthi, Subir Samanta

Abstract:

The worldwide prevalence of H3N2 influenza virus and its increasing resistance to the existing drugs necessitates for the development of an improved/better targeting anti-influenza drug. H3N2 influenza neuraminidase is one of the two membrane-bound proteins belonging to group-2 neuraminidases. It acts as key player involved in viral pathogenicity and hence, is an important target of anti-influenza drugs. Oseltamivir is one of the potent drugs targeting this neuraminidase. In the present work, we have taken subtype N2 neuraminidase as the receptor and probable analogs of oseltamivir as drug molecules to study the protein-drug interaction in anticipation of finding efficient modified candidate compound. Oseltamivir analogs were made by modifying the functional groups using Marvin Sketch software and were docked using Schrodinger-s Glide. Oseltamivir analog 10 was detected to have significant energy value (16% less compared to Oseltamivir) and could be the probable lead molecule. It infers that some of the modified compounds can interact in a novel manner with increased hydrogen bonding at the active site of neuraminidase and it might be better than the original drug. Further work can be carried out such as enzymatic inhibition studies; synthesis and crystallizing the drug-target complex to analyze the interactions biologically.

Keywords: H3N2 Influenza, Neuraminidase, Oseltamiviranalogs, structure based drug designing

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273 Intelligent System for Breast Cancer Prognosis using Multiwavelet Packets and Neural Network

Authors: Sepehr M.H.Jamarani, M.H.Moradi, H.Behnam, G.A.Rezai Rad

Abstract:

This paper presents an approach for early breast cancer diagnostic by employing combination of artificial neural networks (ANN) and multiwaveletpacket based subband image decomposition. The microcalcifications correspond to high-frequency components of the image spectrum, detection of microcalcifications is achieved by decomposing the mammograms into different frequency subbands,, reconstructing the mammograms from the subbands containing only high frequencies. For this approach we employed different types of multiwaveletpacket. We used the result as an input of neural network for classification. The proposed methodology is tested using the Nijmegen and the Mammographic Image Analysis Society (MIAS) mammographic databases and images collected from local hospitals. Results are presented as the receiver operating characteristic (ROC) performance and are quantified by the area under the ROC curve.

Keywords: Breast cancer, neural networks, diagnosis, multiwavelet packet, microcalcification.

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272 ALDH1A1 as a Cancer Stem Cell Marker: Value of Immunohistochemical Expression in Benign Prostatic Hyperplasia, Prostatic Intraepithelial Neoplasia, and Prostatic Adenocarcinoma

Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

Abstract:

Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma.

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271 Attention Multiple Instance Learning for Cancer Tissue Classification in Digital Histopathology Images

Authors: Afaf Alharbi, Qianni Zhang

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The identification of malignant tissue in histopathological slides holds significant importance in both clinical settings and pathology research. This paper presents a methodology aimed at automatically categorizing cancerous tissue through the utilization of a multiple instance learning framework. This framework is specifically developed to acquire knowledge of the Bernoulli distribution of the bag label probability by employing neural networks. Furthermore, we put forward a neural network-based permutation-invariant aggregation operator, equivalent to attention mechanisms, which is applied to the multi-instance learning network. Through empirical evaluation on an openly available colon cancer histopathology dataset, we provide evidence that our approach surpasses various conventional deep learning methods.

Keywords: Attention Multiple Instance Learning, Multiple Instance Learning, transfer learning, histopathological slides, cancer tissue classification.

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270 Quality Based Approach for Efficient Biologics Manufacturing

Authors: Takashi Kaminagayoshi, Shigeyuki Haruyama

Abstract:

To improve the manufacturing efficiency of biologics, such as antibody drugs, a quality engineering framework was designed. Within this framework, critical steps and parameters in the manufacturing process were studied. Identification of these critical steps and critical parameters allows a deeper understanding of manufacturing capabilities, and suggests to process development department process control standards based on actual manufacturing capabilities as part of a PDCA (plan-do-check-act) cycle. This cycle can be applied to each manufacturing process so that it can be standardized, reducing the time needed to establish each new process.

Keywords: Antibody drugs, biologics, manufacturing efficiency, PDCA cycle, quality engineering.

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269 Transcriptomics Analysis on Comparing Non-Small Cell Lung Cancer versus Normal Lung, and Early Stage Compared versus Late-Stages of Non-Small Cell Lung Cancer

Authors: Achitphol Chookaew, Paramee Thongsukhsai, Patamarerk Engsontia, Narongwit Nakwan, Pritsana Raugrut

Abstract:

Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.

Keywords: Bioinformatics, differentially expressed genes, non-small cell lung cancer, transcriptomics.

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268 A Hybrid Feature Selection and Deep Learning Algorithm for Cancer Disease Classification

Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

Abstract:

Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: Cancer classification, feature selection, deep learning, genetic algorithm.

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267 An SVM based Classification Method for Cancer Data using Minimum Microarray Gene Expressions

Authors: R. Mallika, V. Saravanan

Abstract:

This paper gives a novel method for improving classification performance for cancer classification with very few microarray Gene expression data. The method employs classification with individual gene ranking and gene subset ranking. For selection and classification, the proposed method uses the same classifier. The method is applied to three publicly available cancer gene expression datasets from Lymphoma, Liver and Leukaemia datasets. Three different classifiers namely Support vector machines-one against all (SVM-OAA), K nearest neighbour (KNN) and Linear Discriminant analysis (LDA) were tested and the results indicate the improvement in performance of SVM-OAA classifier with satisfactory results on all the three datasets when compared with the other two classifiers.

Keywords: Support vector machines-one against all, cancerclassification, Linear Discriminant analysis, K nearest neighbour, microarray gene expression, gene pair ranking.

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266 A Systems Approach to Gene Ranking from DNA Microarray Data of Cervical Cancer

Authors: Frank Emmert Streib, Matthias Dehmer, Jing Liu, Max Mühlhauser

Abstract:

In this paper we present a method for gene ranking from DNA microarray data. More precisely, we calculate the correlation networks, which are unweighted and undirected graphs, from microarray data of cervical cancer whereas each network represents a tissue of a certain tumor stage and each node in the network represents a gene. From these networks we extract one tree for each gene by a local decomposition of the correlation network. The interpretation of a tree is that it represents the n-nearest neighbor genes on the n-th level of a tree, measured by the Dijkstra distance, and, hence, gives the local embedding of a gene within the correlation network. For the obtained trees we measure the pairwise similarity between trees rooted by the same gene from normal to cancerous tissues. This evaluates the modification of the tree topology due to progression of the tumor. Finally, we rank the obtained similarity values from all tissue comparisons and select the top ranked genes. For these genes the local neighborhood in the correlation networks changes most between normal and cancerous tissues. As a result we find that the top ranked genes are candidates suspected to be involved in tumor growth and, hence, indicates that our method captures essential information from the underlying DNA microarray data of cervical cancer.

Keywords: Graph similarity, DNA microarray data, cancer.

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265 Gene Selection Guided by Feature Interdependence

Authors: Hung-Ming Lai, Andreas Albrecht, Kathleen Steinhöfel

Abstract:

Cancers could normally be marked by a number of differentially expressed genes which show enormous potential as biomarkers for a certain disease. Recent years, cancer classification based on the investigation of gene expression profiles derived by high-throughput microarrays has widely been used. The selection of discriminative genes is, therefore, an essential preprocess step in carcinogenesis studies. In this paper, we have proposed a novel gene selector using information-theoretic measures for biological discovery. This multivariate filter is a four-stage framework through the analyses of feature relevance, feature interdependence, feature redundancy-dependence and subset rankings, and having been examined on the colon cancer data set. Our experimental result show that the proposed method outperformed other information theorem based filters in all aspect of classification errors and classification performance.

Keywords: Colon cancer, feature interdependence, feature subset selection, gene selection, microarray data analysis.

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264 Stability Analysis of Two-delay Differential Equation for Parkinson's Disease Models with Positive Feedback

Authors: M. A. Sohaly, M. A. Elfouly

Abstract:

Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation.

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263 Estimating the Absorbed Dose to THYROID during Chest wall Radiotherapy

Authors: Seid Ali Asghar Terohid, Vahid Fayaz

Abstract:

Thyroid cancer-s overall contribution to the worldwide cancer burden is relatively small, but incidence rates have increased over the last three decades throughout the world. This trend has been hypothesised to reflect a combination of technological advances enabling increased detection, but also changes in environmental factors, including population exposure to ionising radiation from fallout, diagnostic tests and treatment for benign and malignant conditions. The Thyroid dose received apparently shielded by cerrobend blocks was about 8cGy in 100cGy Expose

Keywords: Absorbed Dose, Thyroid, Radiotherapy

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262 Inhibition Effect of Brazilin to Human Bladder Cancer Cell Line T24

Authors: Liansheng Ren, Xihua Yang, Guoping Wang, Hong Zhang, Lili Zhao, Zhenguo Mi

Abstract:

The inhibition effect of brazilin to human bladder tumor cell line T24 in vitro and in vivo was studied. The results of the in vitro experiments showed that brazilin has strong inhibition activity on the target cells. The inhibition ratio of 100 μg/mL brazilin and 100 μg/mL mitomycin to the target cells was 90.90 % and 63.24 % respectively, which showed that brazilin has higher inhibition activity than mitomycin under the same concentration. Brazilin could induce cell apoptosis in T24 cells. Significant antitumor activity of brazilin was also showed in the animals experiments. The life extention rate of 200 mg/mL, 300 mg/kg, and 400 mg/kg brazilin intraperitoneally injected into Balb/c-nu-nu nude mice that with human bladder cancer were 51.50 %, 56.90 %, and 58.42 %(P<0.05). Our study showed that brazilin has significant inhibitory effect on human bladder tumor cell.

Keywords: bladder cancer, brazilin, inhibition, T24 cell line

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