Search results for: breast cancer stem cells (bCSCs)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5217

Search results for: breast cancer stem cells (bCSCs)

3687 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 240
3686 Enhancing the Use of Traditional, Complementary and Alternative Medicines into Global Cancer Treatment and Research

Authors: Alejandro Salicrup, Riacrdo Gelhman, Geetha Gopalakrishna

Abstract:

The main aim of this session is to have a panel to discuss specific steps for the integration of traditional, complementary and alternative medicine (TCAM) with conventional oncology for enhancing treatment practices at the global level, specifically in low-and-middle-income-countries (LMICs). Concrete current and required programs for strengthening Integrative Oncology research in LMICs will also be discussed. Case Studies from Latin America, Asia, Europe and Africa will discuss and highlight 1) What is working regarding treatment practices in integrative oncology in their countries/regions providing concrete examples 2) What is not working on this integration for cancer treatment in their countries/regions with concrete examples and 3) What are the challenges and opportunities for research related to integrative oncology treatment. Discussion will include potential next steps and potential mechanisms to enhance global integrative oncology research aimed to enhance the use of TCAM therapies and strengthening cancer treatment in LMICs.

Keywords: global cancer treatment, integrative oncology research, low and middle income countries, traditional, complementary and alternative medicines

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3685 Creating an Impact through Environmental Law and Policy with a Focus on Environmental Science Restoration with Social Impacts

Authors: Lauren Beth Birney

Abstract:

BOP-CCERS is a consortium of scientists, K-16 New York City students, faculty, academicians, teachers, stakeholders, STEM Industry professionals, CBO’s, NPO’s, citizen scientists, and local businesses working in partnership to restore New York Harbor’s oyster populations while at the same time providing clean water in New York Harbor. BOP-CCERS gives students an opportunity to learn hands-on about environmental stewardship as well as environmental law and policy by giving students real responsibility. The purpose of this REU will allow for the BOP CCERS Project to further broaden its parameters into the focus of environmental law and policy where further change can be affected. Creating opportunities for undergraduates to work collaboratively with graduate students in law and policy and envision themselves in STEM careers in the field of law continues to be of importance in this project. More importantly, creating opportunities for underrepresented students to pursue careers in STEM Education has been a goal of the project over the last ten years. By raising the level of student interest in community-based citizen science integrated into environmental law and policy, a more diversified workforce will be fostered through the momentum of this dynamic program. The continuing climate crisis facing our planet calls for 21st-century skill development that includes learning and innovation skills derived from critical thinking, which will help REU students address the issues of climate change facing our planet. The demand for a climate-friendly workforce will continue to be met through this community-based citizen science effort. Environmental laws and policies play a crucial role in protecting humans, animals, resources, and habitats. Without these laws, there would be no regulations concerning pollution or contamination of our waterways. Environmental law serves as a mechanism to protect the land, air, water, and soil of our planet. To protect the environment, it is crucial that future policymakers and legal experts both understand and value the importance of environmental protection. The Environmental Law and Policy REU provides students with the opportunity to learn, through hands-on work, the skills, and knowledge needed to help foster a legal workforce centered around environmental protection while participating alongside the BOP CCERS researchers in order to gain research experience. Broadening this area to law and policy will further increase these opportunities and permit students to ultimately affect and influence larger-scale change on a global level while further diversifying the STEM workforce. Students’ findings will be shared at the annual STEM Institute at Pace University in August 2022. Basic research methodologies include qualitative and quantitative analysis performed by the research team. Early findings indicate that providing students with an opportunity to experience, explore and participate in environmental science programs such as these enhances their interests in pursuing STEM careers in Law and Policy, with the focus being on providing opportunities for underserved, marginalized, and underrepresented populations.

Keywords: environmental restoration science, citizen science, environmental law and policy, STEM education

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3684 Potential Drug-Drug Interactions at a Referral Hematology-Oncology Ward in Iran: A Cross-Sectional Study

Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

Abstract:

Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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3683 Determinants of Psychological Distress in Teenagers and Young Adults Affected by Cancer: A Systematic Review

Authors: Anna Bak-Klimek, Emily Spencer, Siew Lee, Karen Campbell, Wendy McInally

Abstract:

Background & Significance: Over half of Teenagers and Young Adults (TYAs) say that they experience psychological distress after cancer diagnosis and TYAs with cancer are at higher risk of developing distress compared to other age groups. Despite this there are no age-appropriate interventions to help TYAs manage distress and there is a lack of conceptual understanding of what causes distress in this population group. This makes it difficult to design a targeted, developmentally appropriate intervention. This review aims to identify the key determinants of distress in TYAs affected by cancer and to propose an integrative model of cancer-related distress for TYAs. Method: A literature search was performed in Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, CINAHL, EMBASE and PsycArticles in May-June, 2022. Quantitative literature was systematically reviewed on the relationship between psychological distress experienced by TYAs affected by cancer and a wide range of factors i.e. individual (demographic, psychological, developmental, and clinical factors) and contextual (social/environmental) factors. Evidence was synthesized and correlates were categorized using the Biopsychosocial Model. The full protocol is available from PROSPERO (CRD42022322069) Results: Thirty eligible quantitative studies met criteria for the review. A total of twenty-six studies were cross-sectional, three were longitudinal and one study was a case control study. The evidence on the relationship between the socio-demographic, illness and treatment-related factors and psychological distress is inconsistent and unclear. There is however consistent evidence on the link between psychological factors and psychological distress. For instance, the use of cognitive and defence coping, negative meta-cognitive beliefs, less optimism, a lack of sense of meaning and lower resilience levels were significantly associated with higher psychological distress. Furthermore, developmental factors such as poor self-image, identity issues and perceived conflict were strongly associated with higher distress levels. Conclusions: The current review suggests that psychological and developmental factors such as ineffective coping strategies, poor self-image and identity issues may play a key role in the development of psychological distress in TYAs affected by cancer. The review proposes a Positive Developmental Psychology Model of Distress for Teenagers and Young Adults affected by cancer. The review highlights that implementation of psychological interventions that foster optimism, improve resilience and address self-image may result in reduced distress in TYA’s with cancer.

Keywords: cancer, determinant, psychological distress, teenager and young adult, theoretical model

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3682 The Subcellular Localisation of EhRRP6 and Its Involvement in Pre-Ribosomal RNA Processing in Growth-Stressed Entamoeba histolytica

Authors: S. S. Singh, A. Bhattacharya, S. Bhattacharya

Abstract:

The eukaryotic exosome complex plays a pivotal role in RNA biogenesis, maturation, surveillance and differential expression of various RNAs in response to varying environmental signals. The exosome is composed of evolutionary conserved nine core subunits and the associated exonucleases Rrp6 and Rrp44. Rrp6p is crucial for the processing of rRNAs, other non-coding RNAs, regulation of polyA tail length and termination of transcription. Rrp6p, a 3’-5’ exonuclease is required for degradation of 5’-external transcribed spacer (ETS) released from the rRNA precursors during the early steps of pre-rRNA processing. In the parasitic protist Entamoeba histolytica in response to growth stress, there occurs the accumulation of unprocessed pre-rRNA and 5’ ETS sub fragment. To understand the processes leading to this accumulation, we looked for Rrp6 and the exosome subunits in E. histolytica, by in silico approaches. Of the nine core exosomal subunits, seven had high percentage of sequence similarity with the yeast and human. The EhRrp6 homolog contained exoribonuclease and HRDC domains like yeast but its N- terminus lacked the PMC2NT domain. EhRrp6 complemented the temperature sensitive phenotype of yeast rrp6Δ cells suggesting conservation of biological activity. We showed 3’-5’ exoribonuclease activity of EhRrp6p with in vitro-synthesized appropriate RNAs substrates. Like the yeast enzyme, EhRrp6p degraded unstructured RNA, but could degrade the stem-loops slowly. Furthermore, immunolocalization revealed that EhRrp6 was nuclear-localized in normal cells but was diminished from nucleus during serum starvation, which could explain the accumulation of 5’ETS during stress. Our study shows functional conservation of EhRrp6p in E.histolytica, an early-branching eukaryote, and will help to understand the evolution of exosomal components and their regulatory function.

Keywords: entamoeba histolytica, exosome complex, rRNA processing, Rrp6

Procedia PDF Downloads 185
3681 Effect of Polarized Light Therapy on Oral Mucositis in Cancer Patients Receiving Chemotherapy

Authors: Zakaria Mowafy Emam Mowafy, Hamed Abd Allah Hamed, Marwa Mahmoud Abd-Elmotalb, Andrew Anis Fakhray Mosaad

Abstract:

The purpose of this paper is to determine the efficacy of polarized light therapy for chemotherapy-treated cancer patients who have oral mucositis. Methods of evaluation are the measurement of the WHO oral mucositis scale and the common toxicity criteria scale. Methods: Thirty cancer patients receiving chemotherapy (males and females) who had oral mucositis and ulceration pain, and their ages ranged from 30 to 55 years, were divided into two groups. Group (A), composed of 15 patients, received the Bioptron light therapy (BLT) in addition to the routine medical care of oral mucositis. Group (B) received only the routine medical care of oral mucositis; the duration of the BLT application was 10 minutes applied daily for 30 days. Results and conclusion: Results showed that the application of the BLT had valuable healing effects on oral mucositis in cancer patients receiving chemotherapy, as evidenced by the high decreases of the WHO oral mucositis scale and the common toxicity criteria scale.

Keywords: Bioptron light therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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3680 Incidence of Idiopathic Inflammatory Myopathies and Their Risk of Cancer in Leeds, UK: An 11-year Epidemiological Study

Authors: Benoit Jauniaux, Azzam Ismail

Abstract:

Objectives: The aims were to identify all incident adult cases of idiopathic inflammatory myopathies (IIMs) in the City of Leeds, UK, and to estimate the risk of cancer in IIMs as compared with the general population. Methods: Cases of IIMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex, and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results: Two hundred and six biopsy reports were identified, and after review, 50 incident cases were included in the study between June 2010 and January 2021. Out of the 50 cases, 27 were male, and 23 were female. The mean incidence rate of IIMs in Leeds throughout the study period was 7.42/1 000 000 person years. The proportion of IIMs cases with a confirmed malignancy was 22%. Compared to the general population, the relative risk of cancer was significantly greater in the IIMs population(31.56, P < 0.01). Conclusions: The incidence rate of IIMs in Leeds was consistent with data from previous literature, however, disagreement exists between different methods of IIMs case inclusion due to varying clinical criteria and definitions. IIMs are associated with increased risk of cancer however, the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with IIMs.

Keywords: idiopathic inflammatory myopathies, myositis, polymyositis, dermatomyositis, malignancy, epidemiology, incidence rate, relative risk

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3679 Bacteriophage Lysis Of Physiologically Stressed Listeria Monocytogenes In A Simulated Seafood Processing Environment

Authors: Geevika J. Ganegama Arachchi, Steve H. Flint, Lynn McIntyre, Cristina D. Cruz, Beatrice M. Dias-Wanigasekera, Craig Billington, J. Andrew Hudson, Anthony N. Mutukumira

Abstract:

In seafood processing plants, Listeriamonocytogenes(L. monocytogenes)likely exists in a metabolically stressed state due to the nutrient-deficient environment, processing treatments such as heating, curing, drying, and freezing, and exposure to detergents and disinfectants. Stressed L. monocytogenes cells have been shown to be as pathogenic as unstressed cells. This study investigated lytic efficacy of (LiMN4L, LiMN4p, and LiMN17) which were previouslycharacterized as virulent against physiologically stressed cells of three seafood borne L. monocytogenesstrains (19CO9, 19DO3, and 19EO3).Physiologically compromised cells ofL. monocytogenesstrains were prepared by aging cultures in TrypticaseSoy Broth at 15±1°C for 72 h; heat injuringcultures at 54±1 - 55±1°C for 40 - 60 min;salt-stressing cultures in Milli-Q water were incubated at 25±1°C in darkness for three weeks; and incubating cultures in 9% (w/v) NaCl at 15±1°C for 72 h. Low concentrations of physiologically compromised cells of three L. monocytogenesstrainswere challenged in vitrowith high titre of three phages in separate experiments using Fish Broth medium (aqueous fish extract) at 15 °C in order to mimic the environment of seafood processing plant. Each phage, when present at ≈9 log10 PFU/ml, reduced late exponential phase cells of L. monocytogenes suspended in fish protein broth at ≈2-3 log10 CFU/ml to a non-detectable level (< 10 CFU/ml). Each phage, when present at ≈8.5 log10 PFU/ml, reduced both heat-injured cells present at 2.5-3.6 log10 CFU/ml and starved cells that were showed coccoid shape, present at ≈2-3 log10 CFU/ml to < 10 CFU/ml after 30 min. Phages also reduced salt-stressed cellspresent at ≈3 log10 CFU/ml by > 2 log10. L. monocytogenes (≈8 log10 CFU/ml) were reduced to below the detection limit (1 CFU/ml) by the three successive phage infections over 16 h, indicating that emergence of spontaneous phage resistance was infrequent. The three virulent phages showed high decontamination potential for physiologically stressed L. monocytogenes strains from seafood processing environments.

Keywords: physiologically stressed L. monocytogenes, heat injured, seafood processing environment, virulent phage

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3678 Extraction and Characterization of Ethiopian Hibiscus macranthus Bast Fiber

Authors: Solomon Tilahun Desisa, Muktar Seid Hussen

Abstract:

Hibiscus macranthus is one of family Malvaceae and genus Hibiscus plant which grows mainly in western part of Ethiopia. Hibiscus macranthus is the most adaptable and abundant plant in the nation, which are used as an ornamental plant often a hedge or fence plant, and used as a firewood after harvesting the stem together with the bark, and used also as a fiber for trying different kinds of things by forming the rope. However, Hibiscus macranthus plant fibre has not been commercially exploited and extracted properly. This study of work describes the possibility of mechanical and retting methods of Hibiscus macranthus fibre extraction and characterization. Hibiscus macranthus fibre is a bast fibre which obtained naturally from the stem or stalks of the dicotyledonous plant since it is a natural cellulose plant fiber. And the fibre characterized by studying its physical and chemical properties. The physical characteristics were investigated as follows, including the length of 100-190mm, fineness of 1.0-1.2Tex, diameter under X100 microscopic view 16-21 microns, the moisture content of 12.46% and dry tenacity of 48-57cN/Tex along with breaking extension of 0.9-1.6%. Hibiscus macranthus fiber productivity was observed that 12-18% of the stem out of which more than 65% is primary long fibers. The fiber separation methods prove to decrease of non-cellulose ingredients in the order of mechanical, water and chemical methods. The color measurement also shows the raw Hibiscus macranthus fiber has a natural golden color according to YID1925 and paler look under both retting methods than mechanical separation. Finally, it is suggested that Hibiscus macranthus fibre can be used for manufacturing of natural and organic crop and coffee packages as well as super absorbent, fine and high tenacity textile products.

Keywords: Hibiscus macranthus, bast fiber, extraction, characterization

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3677 Underdiagnosis of Supraclavicular Brachial Plexus Metastasis in the Shadow of Cervical Disc Herniation: Insights from a Lung Cancer Case Study

Authors: Eunhwa Jun

Abstract:

This case report describes the misdiagnosis of a patient who presented with right arm pain as cervical disc herniation. The patient had several underlying conditions, including hypertension, diabetes mellitus, liver cirrhosis, a history of lung cancer with left lower lobe lobectomy, and adjuvant chemoradiotherapy. An external cervical spine MRI revealed central protruding discs at the C4-5-6-7 levels. Despite treatment with medication and epidural blocks, the patient's pain persisted. A C-RACZ procedure was planned, but the patient's pain had worsened before admission. Using ultrasound, a brachial plexus block was attempted, but the brachial plexus eluded clear visualization, hinting at underlying neurological complexities. Chest CT revealed a new, large soft tissue mass in the right supraclavicular region with adjacent right axillary lymphadenopathy, leading to the diagnosis of metastatic squamous cell carcinoma. Palliative radiation therapy and chemotherapy were initiated as part of the treatment plan, and the patient's pain score decreased to 3 out of 10 on the Numeric Rating Scale (NRS), revealing the pain was due to metastatic lung cancer.

Keywords: supraclavicula brachial plexus metastasis, cervical disc herniation, brachial plexus block, metastatic lung cancer

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3676 Proinflammatory Response of Agglomerated TiO2 Nanoparticles in Human-Immune Cells

Authors: Vaiyapuri Subbarayn Periasamy, Jegan Athinarayanan, Ali A. Alshatwi

Abstract:

The widespread use of Titanium oxide nanoparticles (TiO2-NPs), now are found with different physic-chemical properties (size, shape, chemical properties, agglomeration, etc.) in many processed foods, agricultural chemicals, biomedical products, food packaging and food contact materials, personal care products, and other consumer products used in daily life. Growing evidences have been highlighted that there are risks of physico-chemical properties dependent toxicity with special attention to “TiO2-NPs and human immune system”. Unfortunately, agglomeration and aggregation have frequently been ignored in immuno-toxicological studies, even though agglomeration and aggregation would be expected to affect nanotoxicity since it changes the size, shape, surface area, and other properties of the TiO2-NPs. In this present investigation, we assessed the immune toxic effect of TiO2-NPs on human immune cells Total WBC including Lymphocytes (T cells (CD3+), T helper cells (CD3+, CD4+), Suppressor/cytotoxic T cells (CD3+/CD8+) and NK cells (CD3-/CD16+ and CD56+), Monocytes (CD14+, CD3-) and B lymphocytes (CD19+, CD3-) in order to find the immunological response (IL1A, IL1B, IL2 IL-4, IL5 IL-6, IL-10, IL-12, IL-13, IFN-γ, TGF-β, and TNF-a) and redox gene regulation (TNF, p53, BCl-2, CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1)-linking physicochemical properties with special reference to agglomeration of TiO2-NPs. Our findings suggest that TiO2-NPs altered cytokine production, enhanced phagocytic indexing, metabolic stress through specific immune regulatory- genes expression in different WBC subsets and may contribute to pro-inflammatory response. Although TiO2-NPs have great advantages in the personal care products, biomedical, food and agricultural products, its chronic and acute immune-toxicity still need to be assessed carefully with special reference to food and environmental safety.

Keywords: TiO2 nanoparticles, oxidative stress, cytokine, human immune cells

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3675 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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3674 Psychosocial Determinants of Quality of Life After Treatment For Colorectal Cancer - A Systematic Review

Authors: Lakmali Anthony, Madeline Gillies

Abstract:

Purpose: Long-term survivorship in colorectal cancer (CRC) is increasing as mortality decreases, leading to increased focus on patient-reported outcomes such as quality of life (QoL). CRC patients often have decreased QoL even after treatment is complete. This systematic review of the literature aims to identify psychosocial factors associated with decreased QoL in post-treatment CRC patients. Methodology: This systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search was conducted in MEDLINE, EMBASE, and PsychINFO using MeSH headings. The two authors screened studies for relevance and extracted data. Results: Seventeen studies were identified, including 6,272 total participants (mean = 392, 58% male) with a mean age of 60.6 years. The European Organisation for Research and Treatment of Cancer QLQ-C30 was the most common measure of QoL (n=14, 82.3%). Most studies (n=15, 88.2%) found that emotional distress correlated with poor global QoL. This was most commonly measured with the Hospital Anxiety & Depression Scale (n=11, 64.7%). Other psychosocial factors associated with QoL were lack of social support, body image, and financial difficulties. Clinicopathologic determinants included presence of stoma and metastasis. Conclusion: This systematic review provides a summary of the psychosocial determinants of poor QoL in post-treatment CRC patients, as well as the most commonly reported measures of these. An understanding of these potentially modifiable determinants of poor outcome is pivotal to the provision of quality, patient-centred care in surgical oncology.

Keywords: colorectal cancer, cancer surgery, quality of life, oncology, social determinants

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3673 Functional Gene Expression in Human Cells Using Linear Vectors Derived from Bacteriophage N15 Processing

Authors: Kumaran Narayanan, Pei-Sheng Liew

Abstract:

This paper adapts the bacteriophage N15 protelomerase enzyme to assemble linear chromosomes as vectors for gene expression in human cells. Phage N15 has the unique ability to replicate as a linear plasmid with telomeres in E. coli during its prophage stage of life-cycle. The virus-encoded protelomerase enzyme cuts its circular genome and caps its ends to form hairpin telomeres, resulting in a linear human-chromosome-like structure in E. coli. In mammalian cells, however, no enzyme with TelN-like activities has been found. In this work, we show for the first-time transfer of the protelomerase from phage into human and mouse cells and demonstrate recapitulation of its activity in these hosts. The function of this enzyme is assayed by demonstrating cleavage of its target DNA, followed by detecting telomere formation based on its resistance to recBCD enzyme digestion. We show protelomerase expression persists for at least 60 days, which indicates limited silencing of its expression. Next, we show that an intact human β-globin gene delivered on this linear chromosome accurately retains its expression in the human cellular environment for at least 60 hours, demonstrating its stability and potential as a vector. These results demonstrate that the N15 protelomerse is able to function in mammalian cells to cut and heal DNA to create telomeres, which provides a new tool for creating novel structures by DNA resolution in these hosts.

Keywords: chromosome, beta-globin, DNA, gene expression, linear vector

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3672 Application of Gold Nanorods in Cancer Photothermaltherapy

Authors: Mehrnaz Mostafavi

Abstract:

Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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3671 Cytotoxic and Biocompatible Evaluation of Silica Coated Silver Nanoparticle Against Nih-3t3 Cells

Authors: Chen-En Lin, Lih-Rou Rau, Jiunn-Woei Liaw, Shiao-Wen Tsai

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The unique optical properties of plasmon resonance metallic particles have attracted considerable applications in the fields of physics, chemistry and biology. Metal-Enhanced Fluorescence (MEF) effect is one of the useful applications. MEF effect stated that fluorescence intensity can be quenched or be enhanced depending on the distance between fluorophores and the metal nanoparticles. Silver nanoparticles have used widely in antibacterial studies. However, the major limitation for silver nanoparticles (AgNPs) in biomedical application is well-known cytotoxicity on cells. There were numerous literatures have been devoted to overcome the disadvantage. The aim of the study is to evaluate the cytotoxicity and biocompatibility of silica coated AgNPs against NIH-3T3 cells. The results were shown that NIH-3T3 cells started to detach, shrink, become rounded and finally be irregular in shape after 24 h of exposure at 10 µg/ml AgNPs. Besides, compared with untreated cells, the cell viability significantly decreased to 60% and 40% which were exposed to 10 µg/ml and 20 µg/ml AgNPs respectively. The result was consistent with previously reported findings that AgNPs induced cytotoxicity was concentration dependent. However, the morphology and cell viability of cells appeared similar to the control group when exposed to 20 µg/ml of silica coated AgNPs. We further utilized the dark-field hyperspectral imaging system to analysis the optical properties of the intracellular nanoparticles. The image displayed that the red shift of the surface plasmonic resonances band of the enclosed AgNPs further confirms the agglomerate of the AgNPs rather than their distribution in cytoplasm. In conclusion, the study demonstrated the silica coated of AgNPs showed well biocompatibility and significant lower cytotoxicity compared with bare AgNPs.

Keywords: silver nanoparticles, silica, cell viability, morphology

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3670 Antineoplastic Effect of Tridham and Penta Galloyl Glucose in Experimental Mammary Carcinoma Bearing Rats

Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

Abstract:

Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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3669 Effect of Leptin Gene Methylation on Colorectal Cancer Chemoresistance

Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

Abstract:

Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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3668 Frequency of Tube Feeding in Aboriginal and Non-aboriginal Head and Neck Cancer Patients and the Impact on Relapse and Survival Outcomes

Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

Abstract:

Introduction: Head and neck cancer and treatments are known for their profound effect on nutrition and tube feeding is a common requirement to maintain nutrition. Aim: We aimed to evaluate the frequency of tube feeding in Aboriginal and non-Aboriginal patients, and to examine the relapse and survival outcomes in patients who require enteral tube feeding. Methods: We performed a retrospective cohort analysis of 320 head and neck cancer patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. Data collected included patient demographics, tumour features, treatment details, and cancer and survival outcomes. Results: Aboriginal and non-Aboriginal patients required feeding tubes at similar rates (42.5% vs 46.2% respectively), however Aboriginal patients were far more likely to fail to return to oral nutrition, with 26.3% requiring long-term tube feeding versus only 15% of non-Aboriginal patients. In the overall study population, 27.5% required short-term tube feeding, 17.8% required long-term enteral tube nutrition, and 45.3% of patients did not have a feeding tube at any point. Relapse was more common in patients who required tube feeding, with relapses in 42.1% of the patients requiring long-term tube feeding, 31.8% in those requiring a short-term tube, versus 18.9% in the ‘no tube’ group. Survival outcomes for patients who required a long-term tube were also significantly poorer when compared to patients who only required a short-term tube, or not at all. Long-term tube-requiring patients were half as likely to survive (29.8%) compared to patients requiring a short-term tube (62.5%) or no tube at all (63.5%). Patients requiring a long-term tube were twice as likely to die with active disease (59.6%) as patients with no tube (28%), or a short term tube (33%). This may suggest an increased relapse risk in patients who require long-term feeding, due to consequences of malnutrition on cancer and treatment outcomes, although may simply reflect that patients with recurrent disease were more likely to have longer-term swallowing dysfunction due to recurrent disease and salvage treatments. Interestingly long-term tube patients were also more likely to die with no active disease (10.5%) (compared with short-term tube requiring patients (4.6%), or patients with no tube (8%)), which is likely reflective of the increased mortality associated with long-term aspiration and malnutrition issues. Conclusions: Requirement for tube feeding was associated with a higher rate of cancer relapse, and in particular, long-term tube feeding was associated with a higher likelihood of dying from head and neck cancer, but also a higher risk of dying from other causes without cancer relapse. This data reflects the complex effect of head and neck cancer and its treatments on swallowing and nutrition, and ultimately, the effects of malnutrition, swallowing dysfunction, and aspiration on overall cancer and survival outcomes. Tube feeding was seen at similar rates in Aboriginal and non-Aboriginal patient, however failure to return to oral intake with a requirement for a long-term feeding tube was seen far more commonly in the Aboriginal population.

Keywords: head and neck cancer, enteral tube feeding, malnutrition, survival, relapse, aboriginal patients

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3667 Formulation and Characterization of NaCS-PDMDAAC Capsules with Immobilized Chlorella vulgaris for Phycoremediation of Palm Oil Mill Effluent

Authors: Quin Emparan, Razif Harun, Dayang R. A. Biak, Rozita Omar, Michael K. Danquah

Abstract:

Cultivation of immobilized microalgae cells is on the rise for biotechnological applications. In this study, cultivation of Chlorella vulgaris was carried out in the form of suspended free-cell and immobilized cells system. NaCS-PDMDAAC capsules were used to immobilize C. vulgaris. Initially, the synthesized NaCS with C. vulgaris culture were prepared at various concentration of 5- 20% (w/v) using a 6% hardening solution (PDMDAAC) to investigate the capsules' gel stability and suitability for microalgae cells growth. Then, the capsules produced from 15% NaCS with C. vulgaris culture were furthered investigated using 5%, 10%, and 15% (w/v) of PDMDAAC solution. The capsules' gel stability was evaluated through dissolution time and loss of uniform spherical shape of capsules, while suitability for microalgae cells growth was evaluated through the optical density of microalgae. In this study, the 15% NaCS-10% PDMDAAC capsules were found to be the most suitable to sustain the capsules' gel stability and microalgae cells growth in MLA. For that reason, the C. vulgaris immobilized in the 15% NaCS-10% PDMDAAC capsules were further characterized using physicochemical analysis in terms of morphological, carbon (C), hydrogen (H) and nitrogen (N), Fourier transform-infrared (FT-IR), scanning electron microscopy-energy dispersive X-ray (SEM-EDX), zeta potential and Brunauer-Emmet-Teller (BET) analyses. The results revealed that the presence of sulfonates in the synthesized NaCS and NaCS-PDMDAAC capsules without and with C. vulgaris proves that cellulose alcohol group was successfully bonded by sulfo group. Besides that, immobilized microalgae cells have a smaller cell size of 6.29 ± 1.09 µm and zeta potential of -11.93 ± 0.91 mV than suspended free-cells microalgae culture. It can be summarized that immobilization of C. vulgaris in the 15% NaCS-10% PDMDAAC capsules are relevant as a bioremediator for wastewater treatment purposes due to its suitable size of pore and capsules as well as structural and compositional properties.

Keywords: biological capsules, immobilized cultivation, microalgae, physico-chemical analysis

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3666 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Authors: Harish Rajak, Kamlesh Raghuwanshi

Abstract:

Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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3665 Antiviral Activity of Interleukin-11 in Response to Porcine Epidemic Diarrhea Virus Infection

Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

Abstract:

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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3664 Hypoglycaemic and Hypolipidemic Activity of Cassia occidentalis Linn. Stem Bark Extract in Streptozotocin Induced Diabetes

Authors: Manjusha Choudhary

Abstract:

Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.

Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin

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3663 The Influence of Nutritional and Immunological Status on the Prognosis of Head and Neck Cancer

Authors: Ching-Yi Yiu, Hui-Chen Hsu

Abstract:

Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35%, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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3662 Synthesis of Erlotinib Analogues, Conjugation of BSA to Erlotinib Alcohol and Their Anti-Cancer Activity against NSCLC

Authors: Ramalingam Boobalan, Chinpiao Chen, Jui-I. Chiao

Abstract:

A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The key reactions that involved in synthesis are one-pot oxime formation-dehydration for the formation of nitrile, quinazoline ring formation reaction between aniline and o-cyanoaniline via formamidine intermediate, Fe/NH4Cl catalyzed reduction-hetereocyclization-reductive ring opening reaction for the formation of o-aminobenzamide, high yielding seal tube reactions for O-demethylation, sodium iodide substitution, ammonia substitution. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.

Keywords: anti-cancer, BSA, EGFR, Erlotinib

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3661 Genetic Association and Functional Significance of Matrix Metalloproteinase-14 Promoter Variants rs1004030 and rs1003349 in Gallbladder Cancer Pathogenesis

Authors: J. Vinay , Kusumbati Besra, Niharika Pattnaik, Shivaram Prasad Singh, Manjusha Dixit

Abstract:

Gallbladder cancer (GBC) is rare but highly malignant cancer; its prevalence is more in certain geographical regions and ethnic groups, which include the Northern and Eastern states of India. Previous studies in India have reported genetic predisposition as one of the risk factors in GBC pathogenesis. Although the matrix metalloproteinase-14 (MMP14) is a well-known modulator of the tumor microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in the genetic predisposition for GBC is completely unknown. We elucidated the role of MMP14 promoter variants as genetic risk factors and their implications in expression modulation. We screened MMP14 promoter variants association with GBC using Sanger’s sequencing in approximately 300 GBC and 300 control subjects and 26 GBC tissue samples of Indian ethnicity. The immunohistochemistry was used to check the MMP14 protein expression in GBC tissue samples. The role of promoter variants on expression levels was elucidated using a luciferase reporter assay. The variants rs1004030 (p-value = 0.0001) and rs1003349 (p-value = 0.0008) were significantly associated with gallbladder cancer. The luciferase assay in two different cell lines, HEK-293 (p = 0.0006) and TGBC1TKB (p = 0.0036) showed a significant increase in relative luciferase activity in the presence of risk alleles for both the single nucleotide polymorphisms (SNPs). Similarly, genotype-phenotype correlation in patients samples confirmed that the presence of risk alleles at rs1004030 and rs1003349 increased MMP14 expression. Overall, this study unravels the genetic association of MMP14 promoter variants with gallbladder cancer, which may contribute to pathogenesis by increasing its expression.

Keywords: gallbladder cancer, matrix metalloproteinase-14, single nucleotide polymorphism, case control study, genetic association study

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3660 Development and Characterization of Site Specific Peptide Conjugated Polymeric Nanoparticles for Efficient Delivery of Paclitaxel

Authors: Madhu Gupta, Vikas Sharma, Suresh P. Vyas

Abstract:

CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The CD13 receptors were selected as a targeted site and polymeric nanoparticles (NPs) as a targeted delivery system. By combining these, a cyclic NGR (cNGR) peptide ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted-NPs (cNGR-PEG-PTX-NPs) to enhance the intracellular delivery of anticancer drug to tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in Human Umbilical Vein Endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis and higher intracellular uptake. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor.

Keywords: cyclic NGR, CD13 receptor, targeted polymeric NPs, solid tumor, intracellular delivery

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3659 Highly Concentrated Photo Voltaic using Multi-Junction Concentrator Cell

Authors: Oriahi Love Ndidi

Abstract:

High concentration photovoltaic promises a more efficient, higher power output than traditional photovoltaic modules. One of the driving forces of this high system efficiency has been the continuous improvement of III-V multi-junction solar cell efficiencies. Multi-junction solar cells built from III-V semiconductors are being evaluated globally in concentrated photovoltaic systems designed to supplement electricity generation for utility companies. The high efficiency of this III-V multi-junction concentrator cells, with demonstrated efficiency over 40 percent since 2006, strongly reduces the cost of concentrated photovoltaic systems, and makes III-V multi-junction cells the technology of choice for most concentrator systems today.

Keywords: cost of multi-junction solar cell, efficiency, photovoltaic systems, reliability

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3658 Estimation of Effective Radiation Dose Following Computed Tomography Urography at Aminu Kano Teaching Hospital, Kano Nigeria

Authors: Idris Garba, Aisha Rabiu Abdullahi, Mansur Yahuza, Akintade Dare

Abstract:

Background: CT urography (CTU) is efficient radiological examination for the evaluation of the urinary system disorders. However, patients are exposed to a significant radiation dose which is in a way associated with increased cancer risks. Objectives: To determine Computed Tomography Dose Index following CTU, and to evaluate organs equivalent doses. Materials and Methods: A prospective cohort study was carried at a tertiary institution located in Kano northwestern. Ethical clearance was sought and obtained from the research ethics board of the institution. Demographic, scan parameters and CT radiation dose data were obtained from patients that had CTU procedure. Effective dose, organ equivalent doses, and cancer risks were estimated using SPSS statistical software version 16 and CT dose calculator software. Result: A total of 56 patients were included in the study, consisting of 29 males and 27 females. The common indication for CTU examination was found to be renal cyst seen commonly among young adults (15-44yrs). CT radiation dose values in DLP, CTDI and effective dose for CTU were 2320 mGy cm, CTDIw 9.67 mGy and 35.04 mSv respectively. The probability of cancer risks was estimated to be 600 per a million CTU examinations. Conclusion: In this study, the radiation dose for CTU is considered significantly high, with increase in cancer risks probability. Wide radiation dose variations between patient doses suggest that optimization is not fulfilled yet. Patient radiation dose estimate should be taken into consideration when imaging protocols are established for CT urography.

Keywords: CT urography, cancer risks, effective dose, radiation exposure

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