Search results for: testicular cancer
1687 A Two-Week and Six-Month Stability of Cancer Health Literacy Classification Using the CHLT-6
Authors: Levent Dumenci, Laura A. Siminoff
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Health literacy has been shown to predict a variety of health outcomes. Reliable identification of persons with limited cancer health literacy (LCHL) has been proved questionable with existing instruments using an arbitrary cut point along a continuum. The CHLT-6, however, uses a latent mixture modeling approach to identify persons with LCHL. The purpose of this study was to estimate two-week and six-month stability of identifying persons with LCHL using the CHLT-6 with a discrete latent variable approach as the underlying measurement structure. Using a test-retest design, the CHLT-6 was administered to cancer patients with two-week (N=98) and six-month (N=51) intervals. The two-week and six-month latent test-retest agreements were 89% and 88%, respectively. The chance-corrected latent agreements estimated from Dumenci’s latent kappa were 0.62 (95% CI: 0.41 – 0.82) and .47 (95% CI: 0.14 – 0.80) for the two-week and six-month intervals, respectively. High levels of latent test-retest agreement between limited and adequate categories of cancer health literacy construct, coupled with moderate to good levels of change-corrected latent agreements indicated that the CHLT-6 classification of limited versus adequate cancer health literacy is relatively stable over time. In conclusion, the measurement structure underlying the instrument allows for estimating classification errors circumventing limitations due to arbitrary approaches adopted by all other instruments. The CHLT-6 can be used to identify persons with LCHL in oncology clinics and intervention studies to accurately estimate treatment effectiveness.Keywords: limited cancer health literacy, the CHLT-6, discrete latent variable modeling, latent agreement
Procedia PDF Downloads 1781686 Effects of a Bioactive Subfraction of Strobilanthes Crispus on the Tumour Growth, Body Weight and Haematological Parameters in 4T1-Induced Breast Cancer Model
Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob
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Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus
Procedia PDF Downloads 1511685 Association between Neurofibromatosis Type 1 and Breast Sarcoma: A Case Report
Authors: Ines Zemni, Maher Slimane, Jamel Ben Hassouna, Khaled Rahal
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Background: Neurofibromatosis type 1 (NF1) is a genetic disease, which is associated with an increased risk of developing different malignancies including breast cancer. The association between NF1 band breast sarcoma is a rare entity. Herein we present a 25-year-old woman with NF1 who had fibrosarcoma of the left breast. Case presentation: The patient has multiple thoraco-abdominal 'café au lait' spots. Clinical examination showed a lump of the left breast measuring 9 cm of diameter, which was noticed for 6 months. There was a left inguinal mass of 6 cm of diameter. The patient underwent first a left lumpectomy. Histopathological exam revealed a high-grade fibrosarcoma of the left breast measuring 7.5 cm. Three months later, the patient underwent a left mastectomy and excision of the inguinal mass, which was a neurofibroma. An adjuvant chemotherapy and radiation therapy were indicated, but not applied because of the timeout. The patient is now alive after a follow up of 6 years, with no loco-regional recurrence or metastasis. Conclusion: The relationship between NF1 and breast cancer need to be more clarified by further studies. Establishing a specific screening program of these patients may help to make an earlier diagnosis of breast cancer.Keywords: neurofibromatosis, breast, sarcoma, cancer
Procedia PDF Downloads 1211684 Posttraumatic Stress Disorder and Associated Factors among Patients with Prostate Cancer
Authors: Meral Huri, Sedef Şahin
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Post-traumatic stress disorder (PTSD) is characterized by psychiatric symptoms and triggered by a terrifying experience which may immediately effect cognitive, affective, behavioral and social skills of the individual. One of the most common noncutaneous cancer among men is prostate cancer. The incidence of psychological stress is quite common in men with prostate cancer. The aim of the study was to explore the PTSD frequency among prostate cancer and define the relationship between occupational participation, coping skills and level of perceived social support among patients with prostate cancer. Forty patients diagnosed with prostate cancer were included in the study. After dividing the patients into two groups ( study/ control) according to type of tumor, we recorded their characteristics and evaluations differences. We evaluated the demographic information form, Structured Clinical Interview for DSM-IV (SCID- I)- Clinical Version for PTSD, Multidimensional Scale of Perceived Social Support, Styles of Coping Inventory and Canadian Occupational Performance Measure (COPM) before and after 1 month from surgery. The mean age of the study group (n:18) was 65.85.6 years (range: 61-79 years). The mean age of the control group (n: 22) was a little bit higher than the study group with mean age 71.3±6.9 years (range: 60-85 years). There was no statistically significant difference between the groups for age and the other characteristics. According to the results of the study, statistically significant difference was found between the level of PTSD of study and the control group. 22% of study group showed PTSD while 13% of the control group showed PTSD (r: 0.02, p<0.001). The scores of study group and control group showed statistically significant difference in five sub-categories of Styles of Coping Inventory. Patients with prostate cancer showed decreased scores in optimistic, seeking social supports and self-confident approach, while increased scores in helpless and submissive sub-categories than the control group (p<0.001). The scores of Multidimensional Scale of Perceived Social Supports of study group and control group showed statistically significant difference. The total perceived social supports score of the study group was 71.34 ± 0.75 while it was 75.34 ± 0.64 for the control group. Total and the sub-category scores of study group were statistically significant lower than the control group. According to COPM, mean scores of occupational participation of study group for occupational performance were 4.32±2.24 and 7.01±1.52 for the control group, respectively). Mean Satisfaction scores were 3,22±2.31 and 7.45±1.74 for the study and control group, respectively. The patients with prostate cancer and benign prostate hyperplasia (BPH) did not show any statistically difference in activity performance (r:0.87) while patients with prostate cancer showed statistically lower scores than the patients with BPH in activity satisfaction (r:0.02, p<0.001).Psycho-social occupational therapy interventions might help to decrease the prevalence of PTSD by increasing associated factors such as the social support perception, using coping skills and activity participation of patients with prostate cancer.Keywords: activity performance, occupational therapy, posttraumatic stress disorder, prostate cancer
Procedia PDF Downloads 1451683 Application of an Artificial Neural Network to Determine the Risk of Malignant Tumors from the Images Resulting from the Asymmetry of Internal and External Thermograms of the Mammary Glands
Authors: Amdy Moustapha Drame, Ilya V. Germashev, E. A. Markushevskaya
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Among the main problems of medicine is breast cancer, from which a significant number of women around the world are constantly dying. Therefore, the detection of malignant breast tumors is an urgent task. For many years, various technologies for detecting these tumors have been used, in particular, in thermal imaging in order to determine different levels of breast cancer development. These periodic screening methods are a diagnostic tool for women and may have become an alternative to older methods such as mammography. This article proposes a model for the identification of malignant neoplasms of the mammary glands by the asymmetry of internal and external thermal imaging fields.Keywords: asymmetry, breast cancer, tumors, deep learning, thermogram, convolutional transformation, classification
Procedia PDF Downloads 601682 Automatic Early Breast Cancer Segmentation Enhancement by Image Analysis and Hough Transform
Authors: David Jurado, Carlos Ávila
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Detection of early signs of breast cancer development is crucial to quickly diagnose the disease and to define adequate treatment to increase the survival probability of the patient. Computer Aided Detection systems (CADs), along with modern data techniques such as Machine Learning (ML) and Neural Networks (NN), have shown an overall improvement in digital mammography cancer diagnosis, reducing the false positive and false negative rates becoming important tools for the diagnostic evaluations performed by specialized radiologists. However, ML and NN-based algorithms rely on datasets that might bring issues to the segmentation tasks. In the present work, an automatic segmentation and detection algorithm is described. This algorithm uses image processing techniques along with the Hough transform to automatically identify microcalcifications that are highly correlated with breast cancer development in the early stages. Along with image processing, automatic segmentation of high-contrast objects is done using edge extraction and circle Hough transform. This provides the geometrical features needed for an automatic mask design which extracts statistical features of the regions of interest. The results shown in this study prove the potential of this tool for further diagnostics and classification of mammographic images due to the low sensitivity to noisy images and low contrast mammographies.Keywords: breast cancer, segmentation, X-ray imaging, hough transform, image analysis
Procedia PDF Downloads 831681 Biological Significance of Long Intergenic Noncoding RNA LINC00273 in Lung Cancer Cell Metastasis
Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal
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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma
Procedia PDF Downloads 1561680 Hexane Extract of Thymus serpyllum L.: GC-MS Profile, Antioxidant Potential and Anticancer Impact on HepG2 (Liver Carcinoma) Cell Line
Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla
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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line
Procedia PDF Downloads 5171679 Investigation Two Polymorphism of hTERT Gene (Rs 2736098 and Rs 2736100) and miR- 146a rs2910164 Polymorphism in Cervical Cancer
Authors: Hossein Rassi, Alaheh Gholami Roud-Majany, Zahra Razavi, Massoud Hoshmand
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Cervical cancer is multi step disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN)and cervical cancer. In other hand, some of hTERT and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of hTERT genotypes and miR-146a genotypes in cervical cancer. Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of hTERT and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, hTERT ( rs 2736098) GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical cancer in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of hTERT rs 2736098 genotypes and miR-146a rs2910164 genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.Keywords: polymorphism of hTERT gene, miR-146a rs2910164 polymorphism, cervical cancer, virus
Procedia PDF Downloads 3211678 Predicting Survival in Cancer: How Cox Regression Model Compares to Artifial Neural Networks?
Authors: Dalia Rimawi, Walid Salameh, Amal Al-Omari, Hadeel AbdelKhaleq
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Predication of Survival time of patients with cancer, is a core factor that influences oncologist decisions in different aspects; such as offered treatment plans, patients’ quality of life and medications development. For a long time proportional hazards Cox regression (ph. Cox) was and still the most well-known statistical method to predict survival outcome. But due to the revolution of data sciences; new predication models were employed and proved to be more flexible and provided higher accuracy in that type of studies. Artificial neural network is one of those models that is suitable to handle time to event predication. In this study we aim to compare ph Cox regression with artificial neural network method according to data handling and Accuracy of each model.Keywords: Cox regression, neural networks, survival, cancer.
Procedia PDF Downloads 2001677 Cytotoxic Metabolites from Tagetes minuta L. Growing in Saudi Arabia
Authors: Ali A. A. Alqarni, Gamal A. Mohamed, Hossam M. Abdallah, Sabrin R. M. Ibrahim
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Phytochemical investigation of the methanolic extract of aerial parts of Tagetes minuta L. (Family: Asteraceae) using different chromatographic techniques led to the isolation of five compounds; ecliptal (1), scopoletin (2), P-hydroxy benzoic acid (3), patuletin (4), and patuletin-7-O-β-D-glucopyranoside (5) (Figure 1). Their structures were established based on physical, chemical, and spectral data [Ultraviolet (UV), Proton ¹H, Carbon thirteen ¹³C, and Heteronuclear Multiple Bond Correlation (HMBC) NMR], as well as Electrospray Ionization Mass Spectroscopy (ESIMS) and comparison with literature data. Their cytotoxic activity was assessed towards human liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and human colon cancer (HCT116) cancer cell lines using sulphorhodamine B (SRB) assay. It is noteworthy that compound 1 demonstrated a significant cytotoxic potential towards HepG2, MCF7, and HCT116 cells with IC₅₀s ranging from 2.74 to 7.01 μM, compared to doxorubicin (IC₅₀ 0.18, 0.60, and 0.20 μM, respectively), whereas compounds 2, 4, and 5 showed moderate cytotoxic potential with IC50s ranging from 11.71 to 35.64 μM. However, 3 was inactive up to a concentration of 100 μM towards the three tested cancer cell lines.Keywords: Asteraceae, cytotoxicity, metabolites, Tagetes minuta
Procedia PDF Downloads 1631676 Awareness for Air Pollution Impacts on Lung Cancer in Southern California: A Pilot Study for Designed Smartphone Application
Authors: M. Mohammed Raoof, A. Enkhtaivan, H. Aljuaid
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This study follows the design science research methodology to design and implement a smartphone application artifact. The developed artifact was evaluated through three phases. The System Usability Scale (SUS) metric was used for the evaluation. The designed artifact aims to spread awareness about reducing air pollution, decreasing lung cancer development, and checking the air quality status in Southern California Counties. Participants have been drawn for a pilot study to facilitate awareness of air pollution. The study found that smartphone applications have a beneficial effect on the study’s aims.Keywords: air pollution, design science research, indoor air pollution, lung cancer, outdoor air pollution, smartphone application
Procedia PDF Downloads 1191675 Toxicities associated with EBRT and Brachytherapy for Intermediate and High Risk Prostate Cancer, Correlated with Intra-operative Dosing
Authors: Rebecca Dunne, Cormac Small, Geraldine O'Boyle, Nazir Ibrahim, Anisha
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Prostate cancer is the most common cancer among men, excluding non-melanoma skin cancers. It is estimated that approximately 12% of men will develop prostate cancer during their lifetime. Patients with intermediate, high risk, and very-high risk prostate cancer often undergo a combination of radiation treatments. These treatments include external beam radiotherapy with a low-dose rate or high-dose rate brachytherapy boost, often with concomitant androgen deprivation therapy. The literature on follow-up of patients that receive brachytherapy is scarce, particularly follow-up of patients that undergo high-dose rate brachytherapy. This retrospective study aims to investigate the biochemical failure and toxicities associated with triple therapy and external beam radiotherapy given in combination with brachytherapy. Reported toxicities and prostate specific antigen (PSA) were retrospectively evaluated in eighty patients that previously underwent external beam radiotherapy with a low-dose rate or high dose-rate brachytherapy boost. The severity of toxicities were correlated with intra-operative dosing during brachytherapy on ultrasound and CT scan. The results of this study will provide further information for clinicians and patients when considering treatment options.Keywords: toxicities, combination, brachytherapy, intra-operative dosing, biochemical failure
Procedia PDF Downloads 2421674 Development of a Natural Anti-cancer Formulation Which Can Target Triple Negative Breast Cancer Stem Cells
Authors: Samashi Munaweera
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Cancer stem cells (CSC) are responsible for the initiation, extensive proliferation and metastasis of cancer. CSCs, including breast cancer stem cells (bCSCs) have a capacity to generate chemo and radiotherapy resistance heterogeneous population of cells. Over-expressed ABCB1 has been reported as a main reason for drug resistance of CSCs via activating drug efflux pumps by creating pores in the cell membrane. The overall efficiency of chemotherapeutic agents might be enhanced by blocking the ABCB protein efflux pump in the CSC membrane. There is an urgent need to search for persuasive natural drugs which can target CSCs. Anti-cancer properties of Hylocereus undatus on cancer CSCs have not yet been studied. In the present study, the anti-cancer effects of the peel and flesh of H. undatus fruit on bCSCs were evaluated with the aim of developing a marketable anti-cancer nutraceutical formulation. The flesh and peel of H. undatus were freeze-dried and sequentially extracted into four different solvents (hexane, chloroform, ethyl acetate and ethanol). All extracts (eight extracts) were dried under reduced pressure, and different concentrations (12.5-400 µg/mL) were treated on bCSCs isolated from a triple-negative chemo-resistant breast cancer phenotype (MDA-MB-231 cells). Anti-proliferative effects of all extracts and paclitaxel (positive control) were determined by a colorimetric assay (WST-1 based). Since peel-chloroform (IC50= 54.8 µg/mL) and flesh-ethyl acetate (IC50= 150.5 µg/mL) extras exerted a potent anti-proliferative effect at 72 h post-incubation, a combinatorial formulation (CF) was developed with the most active peel-chloroform extract and 20 µg/mL of verapamil (a known ABCB1 drug efflux pump blocker) first time in the world. Anti-proliferative effects and pro-apoptotic effects of CF were confirmed by estimating activated caspase3 and caspase7 levels and apoptotic morphological features in the CF-treated bCSCs compared to untreated and only verapamil (20 µg/mL) treated bCSCs, and CF treated normal mammary epithelial cells (MCF-10A). The antiproliferative effects of CF (16.4 µg/mL) are greater than paclitaxel (19.2 µg/mL) and three folds greater than peel-chloroform extract (IC50= 54.8 µg/mL) on bCSCs while exerting less effects on normal cells (> 400 µg/mL). Collectively, CF can be considered as a potential initiative of a nutraceutical formulation that can target CSCs.Keywords: breast cancer stem cells (bCSCs), Hylocereus undatus, combinatorial formulation (CF), ABCB 1 protein, verapamil
Procedia PDF Downloads 271673 Targeted Delivery of Sustained Release Polymeric Nanoparticles for Cancer Therapy
Authors: Jamboor K. Vishwanatha
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Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin
Procedia PDF Downloads 3251672 Microbiome Role in Tumor Environment
Authors: Chro Kavian
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The studies conducted show that cancer is a disease caused by populations of microbes, a notion gaining traction as the interaction between the human microbiome and the tumor microenvironment (TME) increasingly shows how environment and microbes dictate the progress and treatment of neoplastic diseases. A person’s human microbiome is defined as a collection of bacteria, fungi, viruses, and other microorganisms whose structure and composition influence biological processes like immune system modulation and nutrient metabolism, which, in turn, affect how susceptible a person is to neoplastic diseases, and response to different therapies. Recent reports demonstrated the influence specific microbiome bacterial populations have on the TME, thereby altering tumoral behaviors and the TME’s contributing factors that impact patients' lives. In addition, gut microbes and their SCFA products are important determinants of the inflammatory landscape of tumors and augment anti-tumor immunity, which can influence immunotherapy outcomes. Studies have also found that dysbiosis, or microbial imbalance, correlates with biological processes such as cancer progression, metastasis, and therapy resistance, leading scientists to explore the use of microbiome deficiencies as adjunctive approaches to chemotherapy and other, more traditional treatments. Nonetheless, mental health practitioners struggling to comprehend the existent gap between cancer patients with pronounced resolutive capabilities and the profound clinical impact Microbiome-targeted cancer therapy has been proven to possess.Keywords: microbiome, cancer, tumor, immune system
Procedia PDF Downloads 181671 A Self-Directed Home Yoga Program for Women with Breast Cancer during Chemotherapy
Authors: Hiroko Komatsu, Kaori Yagasaki
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Background: Cancer-related cognitive impairment is a common problem seen in cancer patients undergoing chemotherapy. Physical activity may show beneficial effects on the cognitive function in such patients. Therefore, we have developed a self-directed home yoga program for cancer patients with cognitive symptoms during chemotherapy. This program involves a DVD presenting a combination of yoga courses based on patient preferences to be practiced at home. This study was performed to examine the feasibility of this program. In addition, we also examined changes in cognitive function and quality of life (QOL) in these patients participating in the program. Methods: This prospective feasibility study was conducted in a 500-bed general hospital in Tokyo, Japan. The study population consisted of breast cancer patients undergoing chemotherapy as the initial therapy. This feasibility study used a convenience sample with estimation of recruitment rate in a single facility with the availability of trained nurses and physicians to ensure safe yoga intervention. The aim of the intervention program was to improve cognitive function by means of both physical and mental activation via yoga, consisting of physical practice, breathing exercises, and meditation. Information on the yoga program was provided as a booklet, with an instructor-guided group yoga class during the orientation, and a self-directed home yoga program on DVD with yoga logs. Results: The recruitment rate was 44.7%, and the study population consisted of 18 women with a mean age of 43.9 years. This study showed high rates of retention, adherence, and acceptability of the yoga program. Improvements were only observed in the cognitive aspects of fatigue, and there were serious adverse events during the program. Conclusion: The self-directed home yoga program discussed here was both feasible and safe for breast cancer patients showing cognitive symptoms during chemotherapy. The patients also rated the program as useful, interesting, and satisfactory. Participation in the program was associated with improvements in cognitive fatigue but not cognitive function.Keywords: yoga, cognition, breast cancer, chemotherapy, quality of life
Procedia PDF Downloads 2571670 Challenges in the Management of Her2 Neu Positive Breast Cancer Patients: Real World Data from India
Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala
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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab
Procedia PDF Downloads 1691669 Assessment of the Radiation Absorbed Dose Produced by Lu-177, Ra-223, AC-225 for Metastatic Prostate Cancer in a Bone Model
Authors: Maryam Tajadod
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The treatment of cancer is one of the main challenges of nuclear medicine; while cancer begins in an organ, such as the breast or prostate, it spreads to the bone, resulting in metastatic bone. In the treatment of cancer with radiotherapy, the determination of the involved tissues’ dose is one of the important steps in the treatment protocol. Comparing absorbed doses for Lu-177 and Ra-223 and Ac-225 in the bone marrow and soft tissue of bone phantom with evaluating energetic emitted particles of these radionuclides is the important aim of this research. By the use of MCNPX computer code, a model for bone phantom was designed and the values of absorbed dose for Ra-223 and Ac-225, which are Alpha emitters & Lu-177, which is a beta emitter, were calculated. As a result of research, in comparing gamma radiation for three radionuclides, Lu-177 released the highest dose in the bone marrow and Ra-223 achieved the lowest level. On the other hand, the result showed that although the figures of absorbed dose for Ra and Ac in the bone marrow are near to each other, Ra spread more energy in cortical bone. Moreover, The alpha component of the Ra-223 and Ac-225 have very little effect on bone marrow and soft tissue than a beta component of the lu-177 and it leaves the highest absorbed dose in the bone where the source is located.Keywords: bone metastases, lutetium-177, radium-223, actinium-225, absorbed dose
Procedia PDF Downloads 1121668 Changes in the Lives of Families Having a Child with Cancer
Authors: Ilknur Kahriman, Hacer Kobya Bulut, Birsel C. Demirbag
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Introduction and Aim: One of the most challenging aspects of being parents of a child diagnosed with cancer is to balance their normal family life with the child's health needs and treatment requirements. Cancer covers an important part of family life and gets ahead of other matters. Families mostly feel that everything has changed in their lives with the cancer diagnosis and are obliged to make a number of adjustments in their lives. Their normal family life suddenly begins to include treatments, hospital appointments and hospitalizations. This study is a descriptive research conducted to determine the changes in the lives of families who had a child with cancer. Methods: This study was carried out with 65 families having children diagnosed with cancer in 0-17 age group at outpatient pediatric oncology clinic and polyclinic of a university hospital in Trabzon. Data were collected through survey method from August to November, 2015. In the analysis of the data, numbers, percentage and chi-square test were used. Findings: It was found out that the average age of mothers was 35.33 years, most of them were primary school graduates (44.6%) and housewives (89.2%) and the average age of fathers was 39.30 years, most of them were high school graduates (29.2%) and self-employed (43.8% ). The majority of their children were boys and their average age was 7.74 years and 77% had Acute lymphocytic leukemia (ALL) diagnosis. 87.5% of the mothers who had a child with cancer had increased fears in their lives, 84.4% had increased workload at home, 82.8% had more stressful life and 82.8% felt themselves physically tired. The mothers indicated that their healthy children could not do the social activities they had used to do before (56.5%), they no longer fed their healthy children with the food they loved eating so that the sick child did not aspire (52.3%) and their healthy children were more furious than before (53.2%). As for the fathers, the fundamental change they had was increased workload at home (82.3%), had more stressful life (80.6%) and could no longer allocate time to the activities they had been interested in and done before (77.8%). There was not a significant difference between the sick children gender and the changes in their parents lives. The communication between the mothers and their healthy children were determined to be positively affected in the families in which the sick child's disease duration was under 12 months (X2 = 6.452, p = 0.011). Conclusion: This study showed that parents having a child with cancer had more workload at home, had more stressful lives, could not allocate time to social activities, had increased fears, felt themselves tired and their healthy children became more furious and their social activities reduced.Keywords: child, cancer, changes in lives, family
Procedia PDF Downloads 2241667 Nursing Experience for a Lung Cancer Patient Undergoing First Time Concurrent Chemotherapy and Radiation Therapy
Authors: Hui Ling Chen
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This article describes the experience of caring for a 68-year-old lung cancer patient undergoing the initial stage of concurrent chemotherapy and radiation therapy during the period of October 21 to November 16. In this study, the author collected data through observation, interviews, medical examination, and the use of Roy’s adaptation model as a guide for data collection and assessment. This study confirmed that chemotherapy induced nausea and vomiting, and radiation therapy impaired skin integrity. At the same time, the patient experienced an anxious reaction to the initial cancer diagnosis and the insertion of subcutaneous infusion ports at the start of medical treatment. Similarly, the patient’s wife shares his anxiety, not to mention the feeling of inadequacy from the lack of training in cancer care. In response, the nursing intervention strategy has included keeping the patient and his family informed of his treatment progress, transfer of cancer care knowledge, and providing them with spiritual support. For example, the nursing staff has helped them draw up a mutually agreeable dietary plan that best suits the wife’s cooking skills, provided them with knowledge in pre- and post-radiation skin care, as well as means to cope with nausea and vomiting reactions. The nursing staff has also worked on building rapport with the patient and his spouse, providing them with encouragement, caring attention and companionship. After the patient was discharged from the hospital, the nursing staff followed up with caring phone calls to help the patient and his family make life-style adjustments to normalcy. The author hopes that his distinctive nursing experience can be useful as a reference for the clinical care of lung cancer patients undergoing the initial stage of concurrent chemotherapy and radiation therapy treatment.Keywords: lung cancer, initiate diagnosis, concurrent chemotherapy and radiation therapy, nursing care
Procedia PDF Downloads 1411666 Cytotoxicity of a Short Chain Fatty Acid Histone Deactylase Inhibitor on HCT116 Human Colorectal Carcinoma Cell Line
Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar
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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT
Procedia PDF Downloads 3611665 Mathematical Model of Cancer Growth under the Influence of Radiation Therapy
Authors: Beata Jackowska-Zduniak
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We formulate and analyze a mathematical model describing dynamics of cancer growth under the influence of radiation therapy. The effect of this type of therapy is considered as an additional equation of discussed model. Numerical simulations show that delay, which is added to ordinary differential equations and represent time needed for transformation from one type of cells to the other one, affects the behavior of the system. The validation and verification of proposed model is based on medical data. Analytical results are illustrated by numerical examples of the model dynamics. The model is able to reconstruct dynamics of treatment of cancer and may be used to determine the most effective treatment regimen based on the study of the behavior of individual treatment protocols.Keywords: mathematical modeling, numerical simulation, ordinary differential equations, radiation therapy
Procedia PDF Downloads 4081664 Exploring Coping Strategies among Caregivers of Children Who Have Survived Cancer
Authors: Noor Ismael, Somaya Malkawi, Sherin Al Awady, Taleb Ismael
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Background/Significance: Cancer is a serious health condition that affects individuals’ quality of life during and after the course of this condition. Children who have survived cancer and their caregivers may deal with residual physical, cognitive or social disabilities. There is little research on caregivers’ health and wellbeing after cancer. To the authors’ best knowledge; there is no specific research about how caregivers cope with everyday stressors after cancer. Therefore, this study aimed to explore the coping strategies that caregivers of children who have survived cancer utilize to overcome everyday stressors. Methods: This study utilized a descriptive survey design. The sample consisted of 103 caregivers, who visited the health and wellness clinic at a national cancer center (additional demographics are presented in the results). The sample included caregivers of children who were off cancer treatments for at least two years from the beginning of data collection. The institution’s internal review board approved this study. Caregivers who agreed to participate completed the survey. The survey collected caregiver reported demographic information and the Brief COPE which measures caregivers' frequency of engaging in certain coping strategies. The Brief COPE consisted of 14 coping sub-scales, which are self-distraction, active coping, denial, substance use, use of emotional support, use of instrumental support, behavioral disengagement, venting, positive reframing, planning, humor, acceptance, religion, and self-blame. Data analyses included calculating sub-scales’ scores for the fourteen coping strategies and analysis of frequencies of demographics and coping strategies. Results: The 103 caregivers who participated in this study were 62% mothers, 80% married, 45% finished high school, 50% do not work outside the house, and 60% have low family income. Result showed that religious coping (66%) and acceptance (60%) were the most utilized coping strategies, followed by positive reframing (45%), active coping (44%) and planning (43%). The least utilized coping strategies in our sample were humor (5%), behavioral disengagement (8%), and substance-use (10%). Conclusions: Caregivers of children who have survived cancer mostly utilize religious coping and acceptance in dealing with everyday stressors. Because these coping strategies do not directly solve stressors like active coping and planning coping strategies, it is important to support caregivers in choosing and implementing effective coping strategies. Knowing from our results that some caregivers may utilize substance use as a coping strategy, which has negative health effects on caregivers and their children, there must be direct interventions that target these caregivers and their families.Keywords: caregivers, cancer, stress, coping
Procedia PDF Downloads 1691663 A Qualitative Meta-Synthesis of the Caregiving Experiences of Family Caregivers for Elderly Cancer Patients in China: Implications for Health Social Work
Authors: Longtao He, Han Wu
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Summary: As the need for elder care increases in China due to a growing aging population and, in particular, rising cancer rates, it becomes increasingly important to also support family caregivers, who are often the main source of care. We used a qualitative meta-synthesis to systematically evaluate and integrate the caregiving experiences of family caregivers of elderly cancer patients as revealed by articles published in Chinese journals. Findings: Nine studies are included in the final analysis. The caregiver experiences they describe are synthesized into three primary themes: care needs, care burden, and care gains, with numerous secondary themes. Besides the findings that seem to align with other findings across cultures, we have highlighted three main discoveries from the synthesis that may be quite specific to the Chinese context: 1. more sub-themes related to specific caregiving skills caregivers of cancer patients; 2. a call for health professionals to improve their communication skills with family caregivers; 3. the important role of filial piety. Applications: Our findings can be used to help health social workers and relevant policymakers in China support family caregivers by identifying the education and training required for caregivers, ways to make the most of potential care gains, and ways to ease care burdens.Keywords: cancer, Chinese family caregivers, caregiving skills, care burden, care gains, health social work
Procedia PDF Downloads 1831662 Parental Awareness and Willingness to Vaccinate Adolescent Daughters against Human Papilloma Virus for Cervical Cancer Prevention in Eastern Region of Kenya: Towards Affirmative Action
Authors: Jacinta Musyoka, Wesley Too
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Cervical cancer is the second leading cause of cancer-related deaths in Kenya and the second most common cancer among women, yet preventable following prevention strategies put in place, which includes vaccination with Human Papilloma Virus Vaccine (HPPV) among the young adolescent girls. Kenya has the highest burden of cervical cancer and the leading cause of death among women of reproductive age and is a known frequent type of cancer amongst women. This is expected to double by 2025 if the necessary steps are not taken, which include vaccinating girls between the ages of 9 and 14 and screening women. Parental decision is critical in ensuring that their daughters receive this vaccine. Hence this study sought to establish parental willingness and factors associate with the acceptability to vaccine adolescent daughters against the human papilloma virus for cervical cancer prevention in Machakos County, Eastern Region of Kenya. Method: Cross-sectional study design utilizing a mixed methods approach was used to collect data from Nguluni Health Centre in Machakos County; Matungulu sub-county, Kenya. This study targeted all parents of adolescent girls seeking health care services in the Matungulu sub-county area who were aged 18 years and above. A total of 220 parents with adolescent girls aged 10-14 years were enrolled into the study after informed consent were sought. All ethical considerations were observed. Quantitative data were analyzed using Multivariate regression analysis, and thematic analysis was used for qualitative data related to perceptions of parents on HPVV. Results, conclusions, and recommendations- ongoing. We expect to report findings and articulate contributions based on the study findings in due course before October 2022Keywords: adolescents, human papilloma virus, kenya, parents
Procedia PDF Downloads 1091661 The Relationship between Resilient Qualities and Health Management in Video Testimonials of Adolescents and Young Adults with Cancer
Authors: A. Sainvil, J. Mallela, L. M. Pereira
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Adolescents and young adults (AYA) diagnosed with cancer are tasked with managing their health through treatment, a time when reliance on and independence from parents may change in unexpected ways. Resilience allows patients to cope and manage their own health through treatment, promoting motivation and a healthier lifestyle. The film acts as a source of reflection through the cancer journey, which may have an impact on how patients cope. The current research investigated relationships between resilient linguistic qualities of the video narratives and attitudes toward personal health management. N=24 patients diagnosed between ages 11-18 were recruited. First, participants provided demographic information, then made a video testimonial about their cancer experience. After filming, participants then completed a questionnaire on the perceived benefits for themselves and others for making the video. Videos were transcribed and analyzed for thematic content via codebook and for linguistic qualities, indicating resilience with the use of the Linguistic Inquiry and Word Count Analysis Program (LIWC). Linear regressions were then calculated to explore relationships between resilient qualities, thematic content, and participants’ perceptions of their medical team and willingness to care for themselves. Participants who spoke with greater narrator connectedness were more likely to change their view of their medical team (β=.628 p=.034). When a participant believed that providers were likely to view their video, they were marginally more likely to want to take better care of themselves (β=.367, p=.078). Participants who spoke in depth about their health reported higher intention to take better care of themselves (β=.785, p=.033). AYAs with cancer who showcased certain resilient qualities within their narrative were more likely to consider taking better care of themselves. Additionally, the more patients reflected on their health, the more they wanted to take better care of themselves. These relationships were stronger when a patient believed that a provider would watch their video. Study findings highlight the utility of film in uncovering aspects of resilience and coping that may lead to healthier behaviors in AYAs with cancer.Keywords: adolescents, cancer, resilience, health management
Procedia PDF Downloads 891660 Cultural Barriers in the Communication of Breast Cancer in Sub-Saharan Africa
Authors: Kayum Fokoue Carole
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This paper aims at verifying the effectiveness of reaching target populations while paying attention to their cultural background when communicating new knowledge, ideas or technology in a multicultural world. Our case study is an experiment on the communication of knowledge on breast cancer in three sub-Saharan countries (Ghana, Tchad, and Cameroon health). The methodology consisted of submitting a semi-structured questionnaire to local populations in some localities in these target countries in order to determine the cultural barriers hindering the effective communication of knowledge on breast cancer. Once this done, sensitization documents on breast cancer were translated into Ewe (Ghana), Mbaye (Tchad), Ghomala’, Ewondo, and Fufulde (Cameroon). In each locality, a sensitization programme was organised for two groups. For one group, the cultural barriers discovered were taken into consideration while communicating during the programme whereas in the other group, they were not. Another questionnaire was disseminated after three months to verify the level of appropriation of those who attended the campaign based on Chumbow’s appropriation theory. This paper, therefore, discusses some spiritual beliefs, representations and practices in the target African communities hindering effective communication of issues on breast cancer in the target localities. Findings reveal that only 38% of respondents in the group of those for whom cultural barriers were not taken into account during the programme had a high level of appropriation while for the other group, 86% had a high level of appropriation. This is evidence that the communication of issues on breast cancer can be more effective by reaching different populations in a language they best master while paying attention to their culture. Therefore, international communication of new knowledge should be culturally contextualised. Suggestions at the end of the paper are directed towards the achievement of these goals. The present work promotes international partnership in addressing and resolving global health preoccupations since research findings from one community/country can be mutualized in partnership with other communities and countries.Keywords: cultural barriers, communication, health, breast cancer
Procedia PDF Downloads 3391659 The Importance of Introducing New Academic Programs in Egyptian National Cancer Institute
Authors: Mohammed S. Mohammed, Asmaa M. S. Mohammed
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Background: To achieve the quality of cancer care, the oncologic academic programs should be continuously developed with establishing new ones. We highlighted three disciplines, Clinical nutrition, medical biophysics and radiobiology and Psycho-oncology programs; without a doubt, the Egyptian National Cancer Institute, in the accreditation era, will be establishing them due to their importance in improving the skills of cancer practitioners. Methods: The first suggested program in Clinical Nutrition that is dealing with the assessment of the patient's well-being before, during and after treatment to avoid the defects in the metabolism resulting from the cancer disease and its treatment by giving the supplements in the patient's diet. The second program is Medical Biophysics and Radiobiology, which there's no denying that it is provided in Cairo University as a good program in the faculty of science but lacks the clinical practice. Hence, it is probably better to establish this program in our institute to improve the practitioner skills and introduce a tailored radiation therapy regimen for every patient according to their characteristic profile. While patients are receiving their treatment, the risk of post-traumatic stress disorder arises, so the importance of the third program, Psycho-Oncology, is clearly obtained. This program is concerned with the psychological, social, behavioral, and ethical aspects of cancer. The area of multi-disciplinary interest has boundaries with the major specialties in oncology: the clinical disciplines (surgery, medicine, pediatrics, and radiotherapy), epidemiology, immunology, endocrinology, biology, pathology, bioethics, palliative care, rehabilitation medicine, clinical trials research and decision making, as well as psychiatry and psychology. Results: It is a prospective academic plan which is compatible with the institutional vision and its strategic plan. Conclusion: In this context, evaluating and understanding the suggested academic programs has become a mandatory part of cancer care. And it is essential to be provided by the NCI.Keywords: clinical nutrition, psycho-oncology, medical biophysics and radiobiology, medical education
Procedia PDF Downloads 2361658 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment
Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery
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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking
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