Search results for: anti cancer drug
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5265

Search results for: anti cancer drug

4605 Improved Wetting for Improved Solubility and Dissolution of Candesartan Cilexetil

Authors: Shilpa Bhilegaonkar, Ram Gaud

Abstract:

Candesartan cilexetil is a poorly soluble antihypertensive agent with solubility limited bioavailability (15%). To initiate process of solubilisation, it is very much necessary to displace the air at the surface and wet the drug surface with a solvent, with which drug is compatible. Present research adopts the same principle to improve solubility and dissolution of candesartan cilexetil. Solvents used here are surfactant and modified surfactant in different drug: solvent (1:1-1:9) ratio’s for preparation of adsorbates. Adsorbates were then converted into free flowing powders as liquisolid compacts and compressed to form tablets. Liquisolid compacts were evaluated for improvement in saturation solubility and dissolution of candesartan cilexetil. All systems were evaluated for improvement in saturation solubility and dissolution in different medias such as water, 0.1 N HCl, Phosphate buffer pH 6.8 and media given by office of generic drugs along with other physicochemical testing. All systems exhibited a promising advantage in terms of solubility and dissolution without affecting the drug structure as confirmed by IR and XRD. No considerable advantage was seen of increasing solvent ratio with drug.

Keywords: candesartan cilexetil, improved dissolution, solubility, liquisolid

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4604 The Using of Social Marketing Approach for Conducting Anti-Corruption Campaign: A Review of Literature

Authors: Rosidah Rosidah

Abstract:

The paper aims to identify and examine the effectiveness of social marketing as an approach for conducting anti-corruption campaign. Social marketing has been widely used to promote social change for the benefit of individual and society; such as for promoting healthy foods consumption, encouraging breastfeeding, reducing smoking, solving alcohol problem and drunk driving. Therefore, it is believed that this approach can be promising to be used in anti-corruption campaign. It is because social marketing can be useful of prompting people to act in accordance to the existing norms that denounce corruption, or help to establish new norms that more averse to corruption. It has established into evidence and insight based approaches to social campaign that focus on changing people’s behavior. Qualitative approach will be used in this study, with the using of literature review and secondary data analysis as the research methods. This paper is still on preliminary stage, which its results is expected to provide fundamental basis for designing model of intervention (anti-corruption campaign) using social marketing approaches.

Keywords: anti-corruption campaign, behavioral change, social influence, social marketing

Procedia PDF Downloads 316
4603 Preparation of Bead-On-String Alginate/Soy Protein Isolated Nanofibers via Water-Based Electrospinning and Its Application for Drug Loading

Authors: Patcharakamon Nooeaid, Piyachat Chuysrinuan

Abstract:

Electrospun natural polymers-based nanofibers are one of the most interesting materials used in tissue engineering and drug delivery applications. Bead-on-string nanofibers have gained considerable interest for sustained drug release. Vancomycin was used as the model drug and sodium alginate (SA)/soy protein isolated (SPI) as the polymer blend to fabricate the bead-on-string nanofibers by aqueous-based electrospinning. The bead-on-string SA/SPI nanofibers were successfully fabricated by the addition of poly(ethylene oxide) (PEO) as a co-blending polymer. SA-PEO with mass ratio of 70/30 showed the best spinnability with continuous nanofibers without the occurrence of beads. Bead structure formed with the addition of SPI and bead number increased with increasing SPI content. The electrospinning of 80/20 SA-PEO/SPI was obtained as a great promising bead-on-string nanofibers for drug loading, while the solution of 50/50 was not able to obtain continuous fibers. In vitro release tests showed that a more sustainable release profile up to 14 days with less initial burst release on day 1 could be obtained from the bead-on-string fibers than from smooth fibers with uniform diameter. In addition, vancomycin-loaded beaded fibers inhibited the growth of Staphylococcus aureus (S. aureus) bacteria. Therefore, the SA-PEO/SPI nanofibers showed the potential to be used as biomaterials for tissue engineering and drug delivery.

Keywords: bead-on-string fibers, electrospinning, drug delivery, tissue engineering

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4602 In vitro Study of Laser Diode Radiation Effect on the Photo-Damage of MCF-7 and MCF-10A Cell Clusters

Authors: A. Dashti, M. Eskandari, L. Farahmand, P. Parvin, A. Jafargholi

Abstract:

Breast Cancer is one of the most considerable diseases in the United States and other countries and is the second leading cause of death in women. Common breast cancer treatments would lead to adverse side effects such as loss of hair, nausea, and weakness. These complications arise because these cancer treatments damage some healthy cells while eliminating the cancer cells. In an effort to address these complications, laser radiation was utilized and tested as a targeted cancer treatment for breast cancer. In this regard, tissue engineering approaches are being employed by using an electrospun scaffold in order to facilitate the growth of breast cancer cells. Polycaprolacton (PCL) was used as a material for scaffold fabricating because of its biocompatibility, biodegradability, and supporting cell growth. The specific breast cancer cells have the ability to create a three-dimensional cell cluster due to the spontaneous accumulation of cells in the porosity of the scaffold under some specific conditions. Therefore, we are looking for a higher density of porosity and larger pore size. Fibers showed uniform diameter distribution and final scaffold had optimum characteristics with approximately 40% porosity. The images were taken by SEM and the density and the size of the porosity were determined with the Image. After scaffold preparation, it has cross-linked by glutaraldehyde. Then, it has been washed with glycine and phosphate buffer saline (PBS), in order to neutralize the residual glutaraldehyde. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor (MTT) results have represented approximately 91.13% viability of the scaffolds for cancer cells. In order to create a cluster, Michigan Cancer Foundation-7 (MCF-7, breast cancer cell line) and Michigan Cancer Foundation-10A (MCF-10A, human mammary epithelial cell line) cells were cultured on the scaffold in 24 well plate for five days. Then, we have exposed the cluster to the laser diode 808 nm radiation to investigate the effect of laser on the tumor with different power and time. Under the same conditions, cancer cells lost their viability more than the healthy ones. In conclusion, laser therapy is a viable method to destroy the target cells and has a minimum effect on the healthy tissues and cells and it can improve the other method of cancer treatments limitations.

Keywords: breast cancer, electrospun scaffold, polycaprolacton, laser diode, cancer treatment

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4601 Proniosomes as a Drug Carrier for Topical Delivery of Tolnaftate

Authors: Mona Mahmoud Abou Samra, Alaa Hamed Salama, Ghada Awad, Soheir Said Mansy

Abstract:

Proniosomes are well documented for topical drug delivery and preferred over other vesicular systems because they are biodegradable, biocompatible, non-toxic, possess skin penetration ability and prolong the release of drugs by acting as depot in deeper layers of skin. Proniosome drug delivery was preferred due to improved stability of the system than niosomes. The present investigation aimed at formulation development and performance evaluation of proniosomal gel as a vesicular drug carrier system for antifungal drug tolnaftate. Proniosomes was developed using different nonionic surfactants such as span 60 and span 65 with cholesterol in different molar ratios by the Coacervation phase separation method in presence or absence of either lecithin or phospholipon 80 H. Proniosomal gel formulations of tolnaftate were characterized for vesicular shape & size, entrapment efficiency, rheological properties and release study. The effect of surfactants and additives on the entrapment efficiency, particle size and percent of drug released was studied. The selected proniosomal formulations for topical delivery of tolnaftate was subjected to a microbiological study in male rats infected with Trichophyton rubrum; the main cause of Tinea Pedis compared to the free drug and a market product and the results was recorded.

Keywords: fungal infection, proniosome, tolnaftate, trichophyton rubrum

Procedia PDF Downloads 495
4600 Biomaterials Solutions to Medical Problems: A Technical Review

Authors: Ashish Thakur

Abstract:

This technical paper was written in view of focusing the biomaterials and its various applications in modern industries. Author tires to elaborate not only the medical, infect plenty of application in other industries. The scope of the research area covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. Biomaterials are invariably in contact with living tissues. Thus, interactions between the surface of a synthetic material and biological environment must be well understood. This paper reviews the benefits and challenges associated with surface modification of the metals in biomedical applications. The paper also elaborates how the surface characteristics of metallic biomaterials, such as surface chemistry, topography, surface charge, and wettability, influence the protein adsorption and subsequent cell behavior in terms of adhesion, proliferation, and differentiation at the biomaterial–tissue interface. The chapter also highlights various techniques required for surface modification and coating of metallic biomaterials, including physicochemical and biochemical surface treatments and calcium phosphate and oxide coatings. In this review, the attention is focused on the biomaterial-associated infections, from which the need for anti-infective biomaterials originates. Biomaterial-associated infections differ markedly for epidemiology, aetiology and severity, depending mainly on the anatomic site, on the time of biomaterial application, and on the depth of the tissues harbouring the prosthesis. Here, the diversity and complexity of the different scenarios where medical devices are currently utilised are explored, providing an overview of the emblematic applicative fields and of the requirements for anti-infective biomaterials. In addition to this, chapter introduces nanomedicine and the use of both natural and synthetic polymeric biomaterials, focuses on specific current polymeric nanomedicine applications and research, and concludes with the challenges of nanomedicine research. Infection is currently regarded as the most severe and devastating complication associated to the use of biomaterials. Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. Polymeric nanomaterial-based therapeutics plays a key role in the field of medicine in treatment areas such as drug delivery, tissue engineering, cancer, diabetes, and neurodegenerative diseases. Advantages in the use of polymers over other materials for nanomedicine include increased functionality, design flexibility, improved processability, and, in some cases, biocompatibility.

Keywords: nanomedicine, tissue, infections, biomaterials

Procedia PDF Downloads 245
4599 Expression of Hypoxia-Inducible Transmembrane Carbonic Anhydrases IX, Ca XII and Glut 1 in Ovarian Cancer

Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

Abstract:

Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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4598 Release of Calcein from Liposomes Using Low and High Frequency Ultrasound

Authors: Ghaleb A. Husseini, Salma E. Ahmed, Hesham G. Moussa, Ana M. Martins, Mohammad Al-Sayah, Nasser Qaddoumi

Abstract:

This abstract aims to investigate the use of targeted liposomes as anticancer drug carriers in vitro in combination with ultrasound applied as drug trigger; in order to reduce the side effects caused by traditional chemotherapy. Pegylated liposomes were used to encapsulate calcein and then release this model drug when 20-kHz, 40-kHz, 1-MHz and 3-MHz ultrasound were applied at different acoustic power densities. Fluorescence techniques were then used to measure the percent drug release of calcein from these targeted liposomes. Results showed that as the power density increases, at the four frequencies studied, the release of calcein also increased. Based on these results, we believe that ultrasound can be used to increase the rate and amount of chemotherapeutics release from liposomes.

Keywords: liposomes, calcein release, high frequency ultrasound, low frequency ultrasound, fluorescence techniques

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4597 An Alternative and Complementary Medicine Method in Vulnerable Pediatric Cancer Patients: Yoga

Authors: Ç. Erdoğan, T. Turan

Abstract:

Pediatric cancer patients experience multiple distressing, challenges, physical symptom such as fatigue, pain, sleep disturbance, and balance impairment that continue years after treatment completion. In recent years, yoga is often used in children with cancer to cope with these symptoms. Yoga practice is defined as a unique physical activity that combines physical practice, breath work and mindfulness/meditation. Yoga is an increasingly popular mind-body practice also characterized as a mindfulness mode of exercise. This study aimed to evaluate the impact of yoga intervention of children with cancer. This article planned searching the literature in this field. It has been determined that individualized yoga is feasible and provides benefits for inpatient children, improves health-related quality of life, physical activity levels, physical fitness. After yoga program, children anxiety score decreases significantly. Additionally, individualized yoga is feasible for inpatient children receiving intensive chemotherapy. As a result, yoga is an alternative and complementary medicine that can be safely used in children with cancer.

Keywords: cancer treatment, children, nursing, yoga

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4596 The Influence of Polymorphisms of NER System Genes on the Risk of Colorectal Cancer in the Polish Population

Authors: Ireneusz Majsterek, Karolina Przybylowska, Lukasz Dziki, Adam Dziki, Jacek Kabzinski

Abstract:

Colorectal cancer (CRC) is one of the deadliest cancers. Every year we see an increase in the number of cases, and in spite of intensive research etiology of the disease remains unknown. For many years, researchers are seeking to associate genetic factors with an increased risk of CRC, so far it has proved to be a compelling link between the MMR system of DNA repair and hereditary nonpolyposis colorectal cancers (HNPCC). Currently, research is focused on finding the relationship between the remaining DNA repair systems and an increased risk of developing colorectal cancer. The aim of the study was to determine the relationship between gene polymorphisms Ser835Ser of XPF gene and Gly23Ala of XPA gene–elements of NER DNA repair system, and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. We used blood collected from 110 patients diagnosed with colorectal cancer. The control group consisted of equal number of healthy people. Genotyping was performed by TaqMan method. The obtained results indicate that the genotype 23Gly/Ala of XPA gene is associated with an increased risk of colorectal cancer, while 23Ala/Ala as well as TCT allele of Ser835Ser of XPF gene may reduce the risk of CRC.

Keywords: NER, colorectal cancer, XPA, XPF, polymorphisms

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4595 Effects of Renin Angiotensin Pathway Inhibition on Efficacy of Anti-PD-1/PD-L1 Treatment in Metastatic Cancer

Authors: Philip Friedlander, John Rutledge, Jason Suh

Abstract:

Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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4594 Determination of Cyclic Citrullinated Peptide Antibodies on Quartz Crystal Microbalance Based Nanosensors

Authors: Y. Saylan, F. Yılmaz, A. Denizli

Abstract:

Rheumatoid arthritis (RA) which is the most common autoimmune disorder of the body's own immune system attacking healthy cells. RA has both articular and systemic effects.Until now romatiod factor (RF) assay is used the most commonly diagnosed RA but it is not specific. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are IgG autoantibodies which recognize citrullinated peptides and offer improved specificity in early diagnosis of RA compared to RF. Anti-CCP antibodies have specificity for the diagnosis of RA from 91 to 98% and the sensitivity rate of 41-68%. Molecularly imprinted polymers (MIP) are materials that are easy to prepare, less expensive, stable have a talent for molecular recognition and also can be manufactured in large quantities with good reproducibility. Molecular recognition-based adsorption techniques have received much attention in several fields because of their high selectivity for target molecules. Quartz crystal microbalance (QCM) is an effective, simple, inexpensive approach mass changes that can be converted into an electrical signal. The applications for specific determination of chemical substances or biomolecules, crystal electrodes, cover by the thin films for bind or adsorption of molecules. In this study, we have focused our attention on combining of molecular imprinting into nanofilms and QCM nanosensor approaches and producing QCM nanosensor for anti-CCP, chosen as a model protein, using anti-CCP imprinted nanofilms. For this aim, anti-CCP imprinted QCM nanosensor was characterized by Fourier transform infrared spectroscopy, atomic force microscopy, contact angle measurements and ellipsometry. The non-imprinted nanosensor was also prepared to evaluate the selectivity of the imprinted nanosensor. Anti-CCP imprinted QCM nanosensor was tested for real-time detection of anti-CCP from aqueous solution. The kinetic and affinity studies were determined by using anti-CCP solutions with different concentrations. The responses related with mass shifts (Δm) and frequency shifts (Δf) were used to evaluate adsorption properties and to calculate binding (Ka) and dissociation (Kd) constants. To show the selectivity of the anti-CCP imprinted QCM nanosensor, competitive adsorption of anti-CCP and IgM was investigated.The results indicate that anti-CCP imprinted QCM nanosensor has a higher adsorption capabilities for anti-CCP than for IgM, due to selective cavities in the polymer structure.

Keywords: anti-CCP, molecular imprinting, nanosensor, rheumatoid arthritis, QCM

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4593 Synthesis and Cytotoxic Activity of New Quinazolinone-Based Compounds against Human Breast Cancer Cell Line MCF-7

Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

Abstract:

In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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4592 Activity Antidiarrheal Extract Kedondong Leaf in Balb/C Strain Male Mice Invivo

Authors: Johanrik, Arini Aprilliani, Fikri Haikal, Diyas Yuca, Muhammad A. Latif, Edijanti Goenarwo, Nurita P. Sari

Abstract:

Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein / astrigen, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume. This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kgBW to prove there is anti-diarrhea it makes into six treatment groups, for anti-secretory it makes into five treatment groups and anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kgBW have significant value (p < 0.005). The conclusion from this extracts kedondong leaf research 800 mg/kgBW have pharmacological effects as antidiarrhea on Balb/C strain male mice with a mechanism of action as antisecretory and antimotility.

Keywords: anti-diarrhea, anti-secretory, anti-motility, kedondong leaf

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4591 In-silico Design of Riboswitch Based Potent Inhibitors for Vibrio cholera

Authors: Somdutt Mujwar, Kamal Raj Pardasani

Abstract:

Cholera pandemics are caused by facultative pathogenic Vibrio cholera bacteria persisting in the countries having warmer climatic conditions as well as the presence of large water bodies with huge amount of organic matter, it is responsible for the millions of deaths annually. Presently the available therapy for cholera is Oral Rehydration Therapy (ORT) with an antibiotic drug. Excessive utilization of life saving antibiotics drugs leads to the development of resistance by the infectious micro-organism against the antibiotic drugs resulting in loss of effectiveness of these drugs. Also, many side effects are also associated with the use of these antibiotic drugs. This riboswitch is explored as an alternative drug target for Vibrio cholera bacteria to overcome the problem of drug resistance as well as side effects associated with the antibiotics drugs. The bacterial riboswitch is virtually screened with 24407 legends to get possible drug candidates. The 10 ligands showing best binding with the riboswitch are selected to design a pharmacophore, which can be utilized to design lead molecules by using the phenomenon of bioisosterism.

Keywords: cholera, drug design, ligand, riboswitch, pharmacophore

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4590 In silico Analysis of Differentially Expressed Genes in High-Grade Squamous Intraepithelial Lesion and Squamous Cell Carcinomas Stages of Cervical Cancer

Authors: Rahul Agarwal, Ashutosh Singh

Abstract:

Cervical cancer is one of the women related cancers which starts from the pre-cancerous cells and a fraction of women with pre-cancers of the cervix will develop cervical cancer. Cervical pre-cancers if treated in pre-invasive stage can prevent almost all true cervical squamous cell carcinoma. The present study investigates the genes and pathways that are involved in the progression of cervical cancer and are responsible in transition from pre-invasive stage to other advanced invasive stages. The study used GDS3292 microarray data to identify the stage specific genes in cervical cancer and further to generate the network of the significant genes. The microarray data GDS3292 consists of the expression profiling of 10 normal cervices, 7 HSILs and 21 SCCs samples. The study identifies 70 upregulated and 37 downregulated genes in HSIL stage while 95 upregulated and 60 downregulated genes in SCC stages. Biological process including cell communication, signal transduction are highly enriched in both HSIL and SCC stages of cervical cancer. Further, the ppi interaction of genes involved in HSIL and SCC stages helps in identifying the interacting partners. This work may lead to the identification of potential diagnostic biomarker which can be utilized for early stage detection.

Keywords: cervical cancer, HSIL, microarray, SCC

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4589 Design, Synthesis, and Evaluation of Small Peptides for Managing Inflammation: Inhibition to Substrate Approach

Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

Abstract:

Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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4588 Fabrication of Biosensor Based on Layered Double Hydroxide/Polypyrrole/Carbon Paste Electrode for Determination of Anti-Hypertensive and Prostatic Hyperplasia Drug Terazosin

Authors: Amira M. Hassanein, Nehal A. Salahuddin, Atsunori Matsuda, Toshiaki Hattori, Mona N. Elfiky

Abstract:

New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work. This was achieved by exploring the interesting properties of conductive (Mg/Al) layered double hydroxide- Dodecyl Sulphate/Polypyrrole nanocomposites which were synthesized by in-situ polymerization of pyrrole during the assembly of (Mg/Al) layered double hydroxide, and by employing the anionic surfactant Dodecyl sulphate as a modifier. The morphology and surface area of the nanocomposites changed with the percentage of Pyrrole. Under optimal conditions, the modified carbon paste electrode successfully achieved detection limits of 0.057 and 0.134 nmol.L-1 of Terazosin hydrochloride in pharmaceutical formulation and spiked human serum fluid, respectively. Moreover, the sensors are highly stable, reusable, and free from interference by other commonly present excipients in drug formulations.

Keywords: layered double hydroxide, polypyrrole, terazosin hydrochloride, square-wave adsorptive anodic stripping voltammetry

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4587 The Best Prediction Data Mining Model for Breast Cancer Probability in Women Residents in Kabul

Authors: Mina Jafari, Kobra Hamraee, Saied Hossein Hosseini

Abstract:

The prediction of breast cancer disease is one of the challenges in medicine. In this paper we collected 528 records of women’s information who live in Kabul including demographic, life style, diet and pregnancy data. There are many classification algorithm in breast cancer prediction and tried to find the best model with most accurate result and lowest error rate. We evaluated some other common supervised algorithms in data mining to find the best model in prediction of breast cancer disease among afghan women living in Kabul regarding to momography result as target variable. For evaluating these algorithms we used Cross Validation which is an assured method for measuring the performance of models. After comparing error rate and accuracy of three models: Decision Tree, Naive Bays and Rule Induction, Decision Tree with accuracy of 94.06% and error rate of %15 is found the best model to predicting breast cancer disease based on the health care records.

Keywords: decision tree, breast cancer, probability, data mining

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4586 Cytotoxic Effect of Biologically Transformed Propolis on HCT-116 Human Colon Cancer Cells

Authors: N. Selvi Gunel, L. M. Oktay, H. Memmedov, B. Durmaz, H. Kalkan Yildirim, E. Yildirim Sozmen

Abstract:

Object: Propolis which consists of compounds that are accepted as antioxidant, antimicrobial, antiseptic, antibacterial, anti-inflammatory, anti-mutagenic, immune-modulator and cytotoxic, is frequently used in current therapeutic applications. However, some of them result in allergic side effects, causing consumption to be restricted. Previously our group has succeeded in producing a new biotechnological product which was less allergenic. In this study, we purpose to optimize production conditions of this biologically-transformed propolis and determine the cytotoxic effects of obtained new products on colon cancer cell line (HCT-116). Method: Firstly, solid propolis samples were dissolved in water after weighing, grinding and sizing (sieve-35mesh) and applied 40 kHz/10 min ultrasonication. Samples were prepared according to inoculation with Lactobacillus plantarum in two different proportions (2.5% and 3.5%). Chromatographic analyzes of propolis were performed by UPLC-MS/MS (Waters, Milford, MA) system. Results were analysed by UPLC-MS/MS system MassLynx™ 4.1 software. HCT-116 cells were treated with propolis examples at 25-1000 µg/ml concentrations and cytotoxicity were measured by using WST-8 assay at 24, 48, and 72 hours. Samples with biological transformation were compared with the non-transformed control group samples. Our experiment groups were formed as follows: untreated (group 1), propolis dissolved in water ultrasonicated at 40 kHz/10 min (group 2), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 2.5% L. plantarum L1 strain (group 3), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 3.5% L. plantarum L3 strain (group 4). Obtained data were calculated with Graphpad Software V5 and analyzed by two-way ANOVA test followed by Bonferroni test. Result: As a result of our study, the cytotoxic effect of propolis samples on HCT-116 cells was evaluated. There was a 7.21 fold increase in group 3 compared to group 2 in the concentration of 1000 µg/ml, and it was a 6.66 fold increase in group 3 compared to group 1 at the end of 24 hours. At the end of 48 hours, in the concentration of 500 µg/ml, it was determined 4.7 fold increase in group 4 compared to group 3. At the same time, in the concentration of 750 µg/ml it was determined 2.01 fold increase in group 4 compared to group 3 and in the same concentration, it was determined 3.1 fold increase in group 4 compared to group 2. Also, at the 72 hours, in the concentration of 750 µg/ml, it was determined 2.42 fold increase in group 3 according to group 2 and in the same time, in the concentration of 1000 µg/ml, it was determined 2.13 fold increase in group 4 according to group 2. According to cytotoxicity results, the group which were ultrasonicated at 40 kHz/10min and inoculated 3.5% L. plantarum L3-strain had a higher cytotoxic effect. Conclusion: It is known that bioavailability of propolis is halved in six months. The data obtained from our results indicated that biologically-transformed propolis had more cytotoxic effect than non-transformed group on colon cancer cells. Consequently, we suggested that L. plantarum-transformation provides both reduction of allergenicity and extension of bioavailability period by enhancing healthful polyphenols.

Keywords: bio-transformation, propolis, colon cancer, cytotoxicity

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4585 Nanoparticles in Diagnosis and Treatment of Cancer, and Medical Imaging Techniques Using Nano-Technology

Authors: Rao Muhammad Afzal Khan

Abstract:

Nano technology is emerging as a useful technology in nearly all areas of Science and Technology. Its role in medical imaging is attracting the researchers towards existing and new imaging modalities and techniques. This presentation gives an overview of the development of the work done throughout the world. Furthermore, it lays an idea into the scope of the future use of this technology for diagnosing different diseases. A comparative analysis has also been discussed with an emphasis to detect diseases, in general, and cancer, in particular.

Keywords: medical imaging, cancer detection, diagnosis, nano-imaging, nanotechnology

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4584 Anti-Diabetic Effect of Withania somnifera in Alloxan Induced Diabetic Rabbits

Authors: Farah Ali, Tehreem Fiayyaz, Laeeq Akbar Lodhi, Imran Mirza

Abstract:

The present work was undertaken to investigate effects of various extracts of W. somnifera (WS) for anti-diabetic activity in alloxan induced diabetic rabbits. Animals were divided into nine groups of six rabbits each. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and WS root powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of WS in the doses of 100, 150, 200 mg/kg and its aqueous (AWS) and ethanol extracts (EWS) (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively orally for three weeks (day 1-20 o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was given metformin (200 mg/kg) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3 as compared to normal control (NC) group (1). WS (100, 150, 200 mg/kg, p.o) decreased the fasting serum glucose concentration, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. These results indicate that metformin (reference control), (AWS) and (EWS) significantly antagonized the diabetic effects of alloxan.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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4583 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

Abstract:

Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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4582 Bifidobacterial Postbiotics as Health-Promoting Agents in Dairy Products

Authors: Saba Kamalledin Moghadam, Amir M. Mortazavian, Aziz Homayouni-Rad

Abstract:

In the recent decade, bioactive-enriched foods, as well as natural health products, have caught the intention of the general and health-conscious population. In this regard, naturally occurring beneficial microorganisms have been successfully added to various dairy products during fermentation. Bifidobacteria, known as probiotics with a broad range of bioactivities, are commonly used in the dairy industry to naturally enrich dairy products. These bioactive metabolites are industrially and commercially important due to health-promoting activities on the consumers (e.g., anti-hypertensive, anti-diabetic, anti-oxidative, immune-modulatory, anti-cholesterolemic, or microbiome modulation, etcetera). This review aims to discuss the potential of bifidobacteria for the elaboration of dairy foods with functional properties and added value.

Keywords: dairy, probiotic, postbiotic, bifidobacteria, bifidobacterial postbiotic

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4581 Synthesis of a Library of Substituted Isoquinolines Based on a Triazolization Strategy, and Their Anti-HIV and C-X-C Chemokine Receptor Type 4 Antagonist Activity

Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

Abstract:

Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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4580 A Four-Year Study of Thyroid Carcinoma in Hail Region: Increased Incidence

Authors: Laila Seada, Hanan Oreiby, Fawaz Al Rashid, Ashraf Negm

Abstract:

Background and Objective: In most areas of the world, the incidence of thyroid cancer has been increasing over the last decade, mostly due to a combination of early detection of the neoplasm resulting from sensitive procedures and increased population exposure to radiation and unrecognized carcinogens. Methods: Cases of thyroid cancer have been retrieved from the cancer registry at King Khalid Hospital during the period from August 2012 to April 2016. Age, gender and histopathologic types have been recorded. Results: Thyroid carcinoma ranked as the second most common malignancy in females (25%) after breast cancer (31%). It constituted 20.8% of all newly diagnosed cancer cases. As for males, it ranked the 4th type of malignancy after gastrointestinal cancer, lymphomas and soft tissue sarcomas. Mean age for females and males was 38.7 +/- 13.2 and 60.25 +/- 11.5 years, respectively, and the difference between the two groups was statistically significant (p value = 0.0001). Fifty-five (82%) were papillary carcinomas including 10 follicular variant of papillary (FVPC), and eight papillary micro carcinomas (PMC) and two tall cell/oncocytic variants. Follicular carcinomas constituted two (3.1%), while two (3.1%) were anaplastic, and two (3.1%) were medullary. Conclusion: Thyroid cancer incidence in Hail is ranking as the 2nd most common female malignancy similar to other regions in the Kingdom. However, this high incidence contrasts with much lower rates worldwide.

Keywords: thyroid, hail, papillary, microcarcinoma

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4579 Formulation and Characterization of Drug Loaded Niosomal Gel for Anti-Inflammatory Activity

Authors: Sunil Kamboj, Vipin Saini, Suman Bala, Gaurav Sharma

Abstract:

The main aim of the present research was to encapsulate mefenamic acid in niosomes and incorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin.The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12 h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Keywords: mefenamic acid, niosomal gel, nonionic surfactants, sustained release

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4578 Corruption and Anti-Corruption Policies: The Case of Iraq

Authors: Sarwan Hasan

Abstract:

This article is to investigate the main forms and causes of corruption and provides anti-corruption policies. It is significant to find out how both interact and affect each other. The research focuses particularly on the case study of Iraq from 2003 to 2023. In this way, the main methods of analysis will be the system approach to analyze the relationship of different elements of the political system of Iraq in the context of corruption, the process-tracing method to explain the reasons for corruption, and content analysis of the official documents important for the research topic. Moreover, the SWOT analysis will be used in the part about the anti-corruption policies. This article concludes that the main causes behind corruption in Iraq are power distribution based on muhassasa tayifiya (power apportionment based on ethno-sectarianism), decentralized political system, sectarian division, Iran, and socio-cultural structure. The main forms of corruption in the country are illegal enrichment, using public positions for sectarian agenda, criminal corruption, bribery, political patronage, clientelism, cronyism, nepotism, embezzlement, kickback, extortion, money laundry, speed money, theft, and justice obstruction. The main anti-corruption policies in Iraq are establishing the Commission of Integrity, Board of Supreme Audit, Inspectors General and Parliamentary Committee, Internalization (assistance from foreign actors), economic adjustment and financial reform, and the new anti-corruption program of the new Prime Minister (Mohamed Shiyah al-Sudani).

Keywords: anti-corruption, corruption, Iraq, anti-corruption policies

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4577 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

Abstract:

Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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4576 The Predictors of Head and Neck Cancer-Head and Neck Cancer-Related Lymphedema in Patients with Resected Advanced Head and Neck Cancer

Authors: Shu-Ching Chen, Li-Yun Lee

Abstract:

The purpose of the study was to identify the factors associated with head and neck cancer-related lymphoedema (HNCRL)-related symptoms, body image, and HNCRL-related functional outcomes among patients with resected advanced head and neck cancer. A cross-sectional correlational design was conducted to examine the predictors of HNCRL-related functional outcomes in patients with resected advanced head and neck cancer. Eligible patients were recruited from a single medical center in northern Taiwan. Consecutive patients were approached and recruited from the Radiation Head and Neck Outpatient Department of this medical center. Eligible subjects were assessed for the Symptom Distress Scale–Modified for Head and Neck Cancer (SDS-mhnc), Brief International Classification of Functioning, Disability and Health (ICF) Core Set for Head and Neck Cancer (BCSQ-H&N), Body Image Scale–Modified (BIS-m), The MD Anderson Head and Neck Lymphedema Rating Scale (MDAHNLRS), The Foldi’s Stages of Lymphedema (Foldi’s Scale), Patterson’s Scale, UCLA Shoulder Rating Scale (UCLA SRS), and Karnofsky’s Performance Status Index (KPS). The results showed that the worst problems with body HNCRL functional outcomes. Patients’ HNCRL symptom distress and performance status are robust predictors across over for overall HNCRL functional outcomes, problems with body HNCRL functional outcomes, and activity and social functioning HNCRL functional outcomes. Based on the results of this period research program, we will develop a Cancer Rehabilitation and Lymphedema Care Program (CRLCP) to use in the care of patients with resected advanced head and neck cancer.

Keywords: head and neck cancer, resected, lymphedema, symptom, body image, functional outcome

Procedia PDF Downloads 236