Search results for: breast cancer diagnosis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3849

Search results for: breast cancer diagnosis

3249 In-silico Analysis of Plumbagin against Cancer Receptors

Authors: Arpita Roy, Navneeta Bharadvaja

Abstract:

Cancer is an uncontrolled growth of abnormal cells in the body. It is one of the most serious diseases on which extensive research work has been going on all over the world. Structure-based drug designing is a computational approach which helps in the identification of potential leads that can be used for the development of a drug. Plumbagin is a naphthoquinone derivative from Plumbago zeylanica roots and belongs to one of the largest and diverse groups of plant metabolites. Anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin shows inhibitory effects on multiple cancer-signaling proteins; however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. In this investigation, an attempt to provide structural insights into the binding mode of plumbagin against four cancer receptors using molecular docking was performed. Plumbagin showed minimal energy against targeted cancer receptors, therefore suggested its stability and potential towards different cancers. The least binding energies of plumbagin with COX-2, TACE, and CDK6 are -5.39, -4.93, -and 4.81 kcal/mol, respectively. Comparison studies of plumbagin with different receptors showed that it is a promising compound for cancer treatment. It was also found that plumbagin obeys the Lipinski’s Rule of 5 and computed ADMET properties which showed drug likeliness and improved bioavailability. Since plumbagin is from a natural source, it has reduced side effects, and these results would be useful for cancer treatment.

Keywords: cancer, receptor, plumbagin, docking

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3248 Clinical Feature Analysis and Prediction on Recurrence in Cervical Cancer

Authors: Ravinder Bahl, Jamini Sharma

Abstract:

The paper demonstrates analysis of the cervical cancer based on a probabilistic model. It involves technique for classification and prediction by recognizing typical and diagnostically most important test features relating to cervical cancer. The main contributions of the research include predicting the probability of recurrences in no recurrence (first time detection) cases. The combination of the conventional statistical and machine learning tools is applied for the analysis. Experimental study with real data demonstrates the feasibility and potential of the proposed approach for the said cause.

Keywords: cervical cancer, recurrence, no recurrence, probabilistic, classification, prediction, machine learning

Procedia PDF Downloads 349
3247 Ancelim: Health System Restoration Protocol for Cancer Patients

Authors: Mark Berry

Abstract:

A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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3246 Histopathological Characterization of Prostate Cancer in Saudi Patients

Authors: Nadeem A. Kizilbash

Abstract:

The study aimed to compare the histopathological characterization of prostate cancer using the conventional and 2005 ISUP modified Gleason system. It employed samples from 40 prostate cancer patients employing resection, biopsies and RP. The majority of cases (95%) comprised adenocarcinoma of the prostate. The results showed that there is migration or upgrading of scores to higher values on using the 2005 ISUP modified Gleason system and an increase in a score of 7 in more than 45% of the cases.

Keywords: prostate cancer, conventional gleason grading, 2005 ISUP modified gleason system, histopathology

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3245 Retrospective Study on the Prognosis of Patients with New-Onset Atrial Fibrillation to Evaluate the Risk of Developing Occult Cancer in Absence of Concurrent Chronic Inflammatory Disease

Authors: Helen Huang, Francisco Javier Quesada Ocet, Blanca Quesada Oce, Javier Jimenez Bello, Victor Palanca Gil, Alba Cervero Rubio, Ana Paya Chaume, Alejandro Herreros-Pomares, Fernando Vidal-Vanaclocha, Rafael Paya Serrano, Aurelio Quesada Dorador, Monica Soliman

Abstract:

Background: Cancer favors both the pro-inflammatory state and autonomic dysfunction, two important mechanisms in the genesis of AF. Atrial remodeling might be caused as a result of paraneoplastic conditions or the result of direct expression of neoplasia. Here, we hypothesize that cancer, through inflammatory mediators, may favor the appearance of AF and patients with the first episode of AF could have a higher risk of developing cancer. Method: Data was collected from patients who attended the emergency department of our hospital for the first episode of AF, diagnosed electrocardiographically, between 2010-2015 (n = 712). The minimum follow-up was 2 years, recording the appearance of cancer, total mortality, recurrences of AF and other events. Patients who developed cancer and those who did not during the 2 years after the onset of AF were compared, as well as with the incidence of cancer in Spain in 2012. Results: After 2 years, 35 patients (4.91%) were diagnosed with cancer, with an annual incidence of 2.45%. Hematological neoplasms were the most frequent (34.28%). The cancer group was older (76.68 +/-12.75 years vs 74.16 +/-12.71; p <0.05) and had fewer typical symptoms (palpitations) (33.38% vs 14.28% , p <0.05). The incidence of cancer in Spain during 2012 was 0.46%, much lower than our sample. When comparing the incidence by age, these differences were maintained both in those over 65 years of age and in those under 65 years of age (2.17% vs. 0.28%; 0.28% vs. 0.18% respectively). Discussion: Therefore, a high incidence of cancer in patients with the first episode of AF was observed (the annual incidence of 2.45% after the onset of AF is 6.1 times that of the general population). After the evaluation of patients with AF in their first detected episode, surveillance of the appearance of cancer should be considered in clinical practice.

Keywords: cancer, cardiovascular outcomes, atrial fibrillation, inflammation

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3244 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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3243 Medical Radiation Exposure in a Cohort of Children Diagnosed with Solid Tumors: Single Institution Study 1985-2015

Authors: Robin L. Rohrer

Abstract:

Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

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3242 Self-Assembled Nano Aggregates Based On Polyaspartamide Graft Copolymers for pH-Controlled Release of Doxorubicin

Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim

Abstract:

A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.

Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates

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3241 Therapeutic Potential of Cannabis in Cancer: Advances in Clinical Research and Pharmacogenomic Aspects

Authors: Bouchaïb Gazzaz, Hamid El Amri, Hind Dehbi, Abderraouf Hilali

Abstract:

Medical cannabis has been cultivated and used in many countries around the world. The story of the use of cannabis as a therapeutic agent is difficult to trace, in particular, because the laws regulating its production, distribution, possession, and consumption are relatively recent. Nowadays, in countries where it is authorized, medical cannabis is used in a very wide variety of illnesses and pathologies, particularly in cancer cures. Presently, cannabinoid receptor agonists (like nabilone and dronabinol) are used for reducing chemotherapy induced vomiting. This review aims to discuss a recent finding on the use of therapeutic cannabis in patients with cancer. First, this work addresses the progress made in the use of cannabinoids as therapeutic agent and their application in the treatment of different types of cancer. Secondly, a detailed analysis of the pharmacogenetic aspect of cannabis will be discussed.

Keywords: cannabinoids, endocannabinoids system, cancer treatment, cannabinoid receptors, genetic polymorphism, pharmacogenomics

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3240 Classification of Multiple Cancer Types with Deep Convolutional Neural Network

Authors: Nan Deng, Zhenqiu Liu

Abstract:

Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.

Keywords: bioinformatics, cancer, convolutional neural network, deep leaning, gene expression pattern

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3239 The Effects of Highly Active Antiretroviral Therapy (HAART) on the Expression of Muc1 and P65 in a Cervical Cancer Cell Line, HCS-2

Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

Abstract:

Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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3238 Control of Lymphatic Remodelling by miR-132

Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

Abstract:

Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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3237 Telomerase, a Biomarker in Oral Cancer Cell Proliferation and Tool for Its Prevention at Initial Stage

Authors: Shaista Suhail

Abstract:

As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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3236 Prayer Therapy in a Case of Acute Myeloid Leukemia: The Good, the Bad and the Ugly

Authors: Rubai M. Ochieng

Abstract:

Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

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3235 Cancer Patients' Quality of Life and Fatigue: A Correlational Study

Authors: Abdul-Monim Batiha

Abstract:

Aim: The aim of this study were to correlate Jordanian cancer patients’ quality of life and fatigue with selected variables (age, sex, religion, marital status, level of education, type of cancer, number of people living in the same household, type of radiotherapy, dose of radiotherapy, and hemoglobin level). Background: Radiotherapy and chemotherapy remain devastating agents that altered patients’ normal lives. Methods: A correlational design was used in this study to 80 cancer patients and required radiotherapy treatment using a convenience sampling procedure. Results: No significant differences were found in the relationship between quality of life scores and selected variables. A significant negative relationship was found between quality of life scores and the side effects of radiotherapy treatment. Significant positive relationships were found between fatigue scores measured by Piper Fatigue Scale and cancer complications, and radiotherapy side effects. Conclusion: Cancer patients’ quality of life and fatigue are affected by radiotherapy’s side effects and cancer complications. Implications for Nursing: Nurses should try to prevent and manage the negative side effects of radiotherapy and complications of cancer. Such an initiative would serve to design specific nursing interventions that have the potential to help patients enjoy their lives and perform their activities.

Keywords: cancer patients, piper fatigue scale, fatigue, quality of life, radiotherapy

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3234 Lipid-polymer Nanocarrier Platform Enables X-Ray Induced Photodynamic Therapy against Human Colorectal Cancer Cells

Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

Abstract:

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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3233 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer

Authors: Bhumika Wadhwa, Fayaz Malik

Abstract:

The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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3232 Comparative Study of Various Treatment Positioning Technique: A Site Specific Study-CA. Breast

Authors: Kamal Kaushik, Dandpani Epili, Ajay G. V., Ashutosh, S. Pradhaan

Abstract:

Introduction: Radiation therapy has come a long way over a period of decades, from 2-dimensional radiotherapy to intensity-modulated radiation therapy (IMRT) or VMAT. For advanced radiation therapy, we need better patient position reproducibility to deliver precise and quality treatment, which raises the need for better image guidance technologies for precise patient positioning. This study presents a two tattoo simulation with roll correction technique which is comparable to other advanced patient positioning techniques. Objective: This is a site-specific study is aimed to perform a comparison between various treatment positioning techniques used for the treatment of patients of Ca- Breast undergoing radiotherapy. In this study, we are comparing 5 different positioning methods used for the treatment of ca-breast, namely i) Vacloc with 3 tattoos, ii) Breast board with three tattoos, iii) Thermoplastic cast with three fiducials, iv) Breast board with a thermoplastic mask with 3 tattoo, v) Breast board with 2 tattoos – A roll correction method. Methods and material: All in one (AIO) solution immobilization was used in all patient positioning techniques for immobilization. The process of two tattoo simulations includes positioning of the patient with the help of a thoracic-abdomen wedge, armrest & knee rest. After proper patient positioning, we mark two tattoos on the treatment side of the patient. After positioning, place fiducials as per the clinical borders markers (1) sternum notch (lower border of clavicle head) (2) 2 cm below from contralateral breast (3) midline between 1 & 2 markers (4) mid axillary on the same axis of 3 markers (Marker 3 & 4 should be on the same axis). During plan implementation, a roll depth correction is applied as per the anterior and lateral positioning tattoos, followed by the shifts required for the Isocentre position. The shifts are then verified by SSD on the patient surface followed by radiographic verification using Cone Beam Computed Tomography (CBCT). Results: When all the five positioning techniques were compared all together, the produced shifts in Vertical, Longitudinal and lateral directions are as follows. The observations clearly suggest that the Longitudinal average shifts in two tattoo roll correction techniques are less than every other patient positioning technique. Vertical and lateral Shifts are also comparable to other modern positioning techniques. Concluded: The two tattoo simulation with roll correction technique provides us better patient setup with a technique that can be implemented easily in most of the radiotherapy centers across the developing nations where 3D verification techniques are not available along with delivery units as the shifts observed are quite minimal and are comparable to those with Vacloc and modern amenities.

Keywords: Ca. breast, breast board, roll correction technique, CBCT

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3231 Influence of Iron Content in Carbon Nanotubes on the Intensity of Hyperthermia in the Cancer Treatment

Authors: S. Wiak, L. Szymanski, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

Abstract:

The term ‘cancer’ is given to a collection of related diseases that may affect any part of the human body. It is a pathological behaviour of cells with the potential to undergo abnormal breakdown in the processes that control cell proliferation, differentiation, and death of particular cells. Although cancer is commonly considered as modern disease, there are beliefs that drastically growing number of new cases can be linked to the extensively prolonged life expectancy and enhanced techniques for cancer diagnosis. Magnetic hyperthermia therapy is a novel approach to cancer treatment, which may greatly contribute to higher efficiency of the therapy. Employing carbon nanotubes as nanocarriers for magnetic particles, it is possible to decrease toxicity and invasiveness of the treatment by surface functionalisation. Despite appearing in recent years, magnetic particle hyperthermia has already become of the highest interest in the scientific and medical environment. The reason why hyperthermia therapy brings so much hope for future treatment of cancer lays in the effect that it produces in malignant cells. Subjecting them to thermal shock results in activation of numerous degradation processes inside and outside the cell. The heating process initiates mechanisms of DNA destruction, protein denaturation and induction of cell apoptosis, which may lead to tumour shrinkage, and in some cases, it may even cause complete disappearance of cancer. The factors which have the major impact on the final efficiency of the treatment include temperatures generated inside the tissues, time of exposure to the heating process, and the character of an individual cancer cell type. The vast majority of cancer cells is characterised by lower pH, persistent hypoxia and lack of nutrients, which can be associated to abnormal microvasculature. Since in healthy tissues we cannot observe presence of these conditions, they should not be seriously affected by elevation of the temperature. The aim of this work is to investigate the influence of iron content in iron filled Carbon Nanotubes on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon- ferromagnetic nanocontainers (FNCs) includes the synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, radio frequency field

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3230 Diagnosis of the Lubrification System of a Gas Turbine Using the Adaptive Neuro-Fuzzy Inference System

Authors: H. Mahdjoub, B. Hamaidi, B. Zerouali, S. Rouabhia

Abstract:

The issue of fault detection and diagnosis (FDD) has gained widespread industrial interest in process condition monitoring applications. Accordingly, the use of neuro-fuzzy technic seems very promising. This paper treats a diagnosis modeling a strategic equipment of an industrial installation. We propose a diagnostic tool based on adaptive neuro-fuzzy inference system (ANFIS). The neuro-fuzzy network provides an abductive diagnosis. Moreover, it takes into account the uncertainties on the maintenance knowledge by giving a fuzzy characterization of each cause. This work was carried out with real data of a lubrication circuit from the gas turbine. The machine of interest is a gas turbine placed in a gas compressor station at South Industrial Centre (SIC Hassi Messaoud Ouargla, Algeria). We have defined the zones of good and bad functioning, and the results are presented to demonstrate the advantages of the proposed method.

Keywords: fault detection and diagnosis, lubrication system, turbine, ANFIS, training, pattern recognition

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3229 Community Perception and Knowledge on Oral Cancer Screening Methods in Kuwait

Authors: Lavanya Dharmendran, Shenuka Singh, Sona Baburathanam

Abstract:

The aim of the study is to understand the level of awareness in a community of a specific region of Kuwait regarding oral cancer and its screening methods so as to enhance the uptake of oral cancer screening methods. This is a cross-sectional study comprising 100 adult participants residing in the governate of Farwaniya, Kuwait. Participants of above 18 years of both genders will be selected using convenience sampling. Data collection includes the administration of a self-administered questionnaire. The questionnaire comprises three sections, each section assessing the knowledge, attitudes and practices of the participants’ opinions about oral cancer and screening methods. Data will be analyzed using Humphris Oral Cancer Knowledge Scale. Inferential statistics will be done using Chi-Square or Fisher’s exact test for categorical data. A level of p<.05 will be established as being significant. All ethical considerations, such as respect for personal confidentiality and informed consent, will be applied in this study. This study revealed that although respondents were aware of the term oral cancer, more than half of the study participants were unaware of the symptoms associated with this condition. Smoking and alcohol were identified as risk factors for oral cancer, but the majority of participants did not identify the Human Papilloma Virus (HPV) as an added risk factor. This suggests a greater need for dental practitioners to include educational strategies in routine dental visits to ensure greater awareness of oral cancer.

Keywords: oral cancer, oral screening, oral public health, oral health

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3228 Cervical Cell Classification Using Random Forests

Authors: Dalwinder Singh, Amandeep Verma, Manpreet Kaur, Birmohan Singh

Abstract:

The detection of pre-cancerous changes using a Pap smear test of cervical cell is the important step for the early diagnosis of cervical cancer. The Pap smear test consists of a sample of human cells taken from the cervix which are analysed to detect cancerous and pre-cancerous stage of the given subject. The manual analysis of these cells is labor intensive and time consuming process which relies on expert cytotechnologist. In this paper, a computer assisted system for the automated analysis of the cervical cells has been proposed. We propose a morphology based approach to the nucleus detection and segmentation of the cytoplasmic region of the given single or multiple overlapped cell. Further, various texture and region based features are calculated from these cells to classify these into normal and abnormal cell. Experimental results on public available dataset show that our system has achieved satisfactory success rate.

Keywords: cervical cancer, cervical tissue, mathematical morphology, texture features

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3227 Evaluation of the Role of Circulating Long Non-Coding RNA H19 as a Promising Biomarker in Plasma of Patients with Gastric Cancer

Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr

Abstract:

Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.

Keywords: biomarker, gastric, cancer, LncRNA

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3226 Design and Synthesis of Some Oxadiazole Bearing Benzimidazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors

Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

Abstract:

Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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3225 Association of Selected Polymorphisms of BER Pathway with the Risk of Colorectal Cancer in the Polish Population

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

Abstract:

The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphisms Pro242Arg of PolB gene and Arg780His of Lig3 gene 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 780Arg/His of Lig3 gene is associated with an increased risk of colorectal cancer. On the basis of these results, we conclude that Lig3 gene polymorphism Arg780His may be associated with an increased risk of colorectal cancer.

Keywords: BER, colorectal cancer, PolB, Lig3, polymorphisms

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3224 Inverse Problem Method for Microwave Intrabody Medical Imaging

Authors: J. Chamorro-Servent, S. Tassani, M. A. Gonzalez-Ballester, L. J. Roca, J. Romeu, O. Camara

Abstract:

Electromagnetic and microwave imaging (MWI) have been used in medical imaging in the last years, being the most common applications of breast cancer and stroke detection or monitoring. In those applications, the subject or zone to observe is surrounded by a number of antennas, and the Nyquist criterium can be satisfied. Additionally, the space between the antennas (transmitting and receiving the electromagnetic fields) and the zone to study can be prepared in a homogeneous scenario. However, this may differ in other cases as could be intracardiac catheters, stomach monitoring devices, pelvic organ systems, liver ablation monitoring devices, or uterine fibroids’ ablation systems. In this work, we analyzed different MWI algorithms to find the most suitable method for dealing with an intrabody scenario. Due to the space limitations usually confronted on those applications, the device would have a cylindrical configuration of a maximum of eight transmitters and eight receiver antennas. This together with the positioning of the supposed device inside a body tract impose additional constraints in order to choose a reconstruction method; for instance, it inhabitants the use of well-known algorithms such as filtered backpropagation for diffraction tomography (due to the unusual configuration with probes enclosed by the imaging region). Finally, the difficulty of simulating a realistic non-homogeneous background inside the body (due to the incomplete knowledge of the dielectric properties of other tissues between the antennas’ position and the zone to observe), also prevents the use of Born and Rytov algorithms due to their limitations with a heterogeneous background. Instead, we decided to use a time-reversed algorithm (mostly used in geophysics) due to its characteristics of ignoring heterogeneities in the background medium, and of focusing its generated field onto the scatters. Therefore, a 2D time-reversed finite difference time domain was developed based on the time-reversed approach for microwave breast cancer detection. Simultaneously an in-silico testbed was also developed to compare ground-truth dielectric properties with corresponding microwave imaging reconstruction. Forward and inverse problems were computed varying: the frequency used related to a small zone to observe (7, 7.5 and 8 GHz); a small polyp diameter (5, 7 and 10 mm); two polyp positions with respect to the closest antenna (aligned or disaligned); and the (transmitters-to-receivers) antenna combination used for the reconstruction (1-1, 8-1, 8-8 or 8-3). Results indicate that when using the existent time-reversed method for breast cancer here for the different combinations of transmitters and receivers, we found false positives due to the high degrees of freedom and unusual configuration (and the possible violation of Nyquist criterium). Those false positives founded in 8-1 and 8-8 combinations, highly reduced with the 1-1 and 8-3 combination, being the 8-3 configuration de most suitable (three neighboring receivers at each time). The 8-3 configuration creates a region-of-interest reduced problem, decreasing the ill-posedness of the inverse problem. To conclude, the proposed algorithm solves the main limitations of the described intrabody application, successfully detecting the angular position of targets inside the body tract.

Keywords: FDTD, time-reversed, medical imaging, microwave imaging

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3223 Stories of Women With Cervical Cancer in Taiwan: A Narrative Analysis Research

Authors: Pei-Yu Lee

Abstract:

This study investigates the life experience and self-interpretation of female cervical cancer patients under Taiwanese cultural context. Through a Narrative Analysis Research approach, the study took six cervical cancer female patients with an average age of 58 years (ranging from 55-66 years) for an average of twice, 60 minutes each time, in-depth recorded interviews under their consent. After converting the interview recordings into transcripts, the study applied the Riessman approach to analyze the contents. The results revealed two major theme, including 1. The symbolic meaning of the cervix, and 2. Women's perseverance and compliance. Because of the illness metaphor of cervical cancer and the designation of women being family caregivers under the Chinese patriarchal culture, females with cervical cancer are not only patients but also responsible for being family and partner roles, in which contradictions of intimate relationships exist. Show the strength of perseverance and compliance in the course of life. On the other hand, they have to identify and recognize their roles in life and strive to determine the situation of coexisting with the disease to picture their life. The results showed that female cervical cancer patients not only need to combat the disease but also stand against the stigma and the traditional responsibility given to women. The researchers recommend that nurses should include cultural implications in their care of female cervical cancer patients.

Keywords: female, cervical cancer, narrative analysis research, taiwan

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3222 Early Cell Cultures Derived from Human Prostate Cancer Tissue Express Tissue-Specific Epithelial and Cancer Markers

Authors: Vladimir Ryabov, Mikhail Baryshevs, Mikhail Voskresenskey, Boris Popov

Abstract:

The human prostate gland (PG) samples were obtained from patients who had undergone radical prostatectomy for prostate cancer (PC) and used to extract total RNA and prepare the prostate stromal cell cultures (PSCC) and patients-derived organoids (PDO). Growth of the cell cultures was accessed under microscopic evaluation in transmitted light and the marker expression by reverse polymerase chain reaction (RT-PCR), immunofluorescence, and immunoblotting. Some PCR products from prostate tissue, PSCC, and PDO were cloned and sequenced. We found that the cells of early and late passages of PSCC and corresponding PDO expressed luminal (androgen receptor, AR; cytokeratin 18, CK18) and basal (CK5, p63) epithelial markers, the production of which decreased or disappeared in late PSCC and PDO. The PSCC and PDO of early passages from cancer tissue additionally produced cancer markers AMACR, TMPRSS2-ERG, and Ezh2. The expression of TMPRSS2-ERG fusion transcripts was verified by cloning and sequencing the PCR products. The results obtained suggest that early passages of PSCC might be used as a pre-clinical model for the evaluation of early markers of prostate cancer.

Keywords: localized prostate cancer, prostate epithelial markers, prostate cancer markers, AMACR, TMPRSS2-ERG, prostate stromal cell cultures, PDO

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3221 Inhibitory Effect of 13-Butoxyberberine Bromide on Metastasis of Skin Cancer A431 Cells

Authors: Phuriwat Laomethakorn, Siritron Samosorn, Ramida Watanapokasin

Abstract:

Cancer metastasis is the major cause of cancer-related death. Therefore searching for a compound that could inhibit cancer metastasis is necessary. 13-Butoxyberberine bromide is a berberine derivative that has not been reported an anti-metastatic effect on skin cancer cells. This study aimed to investigate the anti-metastatic effect of 13-butoxyberberine bromide on skin cancer A431 cells. The effect of 13-butoxyberberine bromide on A431 cell viability was examined by MTT assay. Suppression of cell migration and invasion in A431 cells were determined by wound healing assay, transwell migration assay, and transwell invasion assay. Metastasis proteins were determined by western blotting. The results demonstrated that 13-butoxyberberine bromide decreased A431 cell viability in a dose-dependent manner. In addition, sub-toxic concentrations of 13-butoxyberberine bromide suppressed cell migration and invasion in A431 cells. In addition, 13-butoxyberberine bromide showed anti-metastatic effects by down-regulated MMP-2 and MMP-9 expression. These findings may be useful in the development of 13-butoxyberberine bromide as an anti-metastatic drug in the future.

Keywords: 13-butoxyberberine bromide, metastasis, skin cancer, MMP

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3220 Cytotoxic Effect of Crude Extract of Sea Pen Virgularia gustaviana on HeLa and MDA-MB-231 Cancer Cell Lines

Authors: Sharareh Sharifi, Pargol Ghavam Mostafavi, Ali Mashinchian Moradi, Mohammad Hadi Givianrad, Hassan Niknejad

Abstract:

Marine organisms such as soft coral, sponge, ascidians, and tunicate containing rich source of natural compound have been studied in last decades because of their special chemical compounds with anticancer properties. The aim of this study was to investigate anti-cancer property of ethyl acetate extracted from marine sea pen Virgularia gustaviana found from Persian Gulf coastal (Bandar Abbas). The extraction processes were carried out with ethyl acetate for five days. Thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) were used for qualitative identification of crude extract. The viability of HeLa and MDA-Mb-231 cancer cells was investigated using MTT assay at the concentration of 25, 50, and a 100 µl/ml of ethyl acetate is extracted. The crude extract of Virgularia gustaviana demonstrated ten fractions with different Retention factor (Rf) by TLC and Retention time (Rt) evaluated by HPLC. The crude extract dose-dependently decreased cancer cell viability compared to control group. According to the results, the ethyl acetate extracted from Virgularia gustaviana inhibits the growth of cancer cells, an effect which needs to be further investigated in the future studies.

Keywords: anti-cancer, Hela cancer cell, MDA-Md-231 cancer cell, Virgularia gustavina

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