Search results for: breast cancer cell lines (MCF7
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5913

Search results for: breast cancer cell lines (MCF7

5703 Comparative in silico and in vitro Study of N-(1-Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent

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

Abstract:

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

Keywords: Doxorubicin, auto dock, in silco, in vitro

Procedia PDF Downloads 392
5702 Comparison of Breast Surface Doses for Full-Field Digital Mammography and Digital Breast Tomosynthesis Using Breast Phantoms

Authors: Chia-Hui Chen, Chien-Kuo Wang

Abstract:

Background: Full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Hence, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Aim: To compare the surface radiation dose (ESD) of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) by using breast phantoms. Method: We analyzed the average entrance surface dose (ESD) of FFDM and DBT by using breast phantoms. Optically Stimulated luminescent Dosimeters (OSLD) were placed in a tissue-equivalent Breast phantom at difference sites of interest. Absorbed dose measurements were obtained after digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) exposures. Results: An automatic exposure control (AEC) is proposed for surface dose measurement during DBT and FFDM. The mean ESD values for DBT and FFDM were 6.37 mGy and 3.51mGy, respectively. Using of OSLD measured for surface dose during DBT and FFDM. There were 19.87 mGy and 11.36 mGy, respectively. The surface exposure dose of DBT could possibly be increased by two times with FFDM. Conclusion: The radiation dose from DBT was higher than that of FFDM and the difference in dose between AEC and OSLD measurements at phantom surface.

Keywords: full-field digital mammography, digital breast tomosynthesis, optically stimulated luminescent dosimeters, surface dose

Procedia PDF Downloads 392
5701 Evaluation of Anti-Cancer Activities of Formononetin in Lung Cancer by in vitro Methods

Authors: Vishnu Varthan Vaithiyalingam Jagannathan, Lakshmi Karunanidhi Santhanalakshmi, Srividya Ammayappan Rajam

Abstract:

Formononetin is the O-Methoxy Flavonol that has many pharmacological activities, which belongs to the flavonoid family. In the current study, activity of this molecule was evaluated in lung cancer cell lines. In general, flavonoids possess certain anticancer mechanism. Being a flavonoid subfamily, this molecule was subjected to evaluate cytotoxicity assay by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)) stain, mode of cell death assay stained by acridine orange and ethidium bromide and Evaluation of Apoptosis pathway (extrinsic or intrinsic) by Caspase 3/7 stain and Rhodamine-123 stain. From the results, we could able to confirm that the investigatory molecule formononetin has anticancer activity and in future, the study will propose to evaluate the formononetin action against genetic changes occurs during lung cancer progression.

Keywords: Caspase 3/7, formononetin, lung cancer, Rhodamine-123

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5700 Satureja bachtiarica Bunge Induce Apoptosis via Mitochondrial Intrinsic Pathway and G1 Cell Cycle Arrest

Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

Abstract:

Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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5699 The Influence of Polysaccharide Isolated from Morinda citrifolia Fruit to the Growth of Vero, He-La and T47D Cell Lines against Doxorubicin in vitro

Authors: Ediati Budi Cahyono, Triana Hertiani, Nauval Arrazy Asawimanda, Wahyu Puji Pratomo

Abstract:

Background: Doxorubicin is widely used as a chemotherapeutic drug despite having many side effects. It may cause macrophage dysfunction and decreasing proliferation of lymphocyte. Noni (Morinda citrifolia) fruit which has rich of polysaccharide content has potential as antitumor and immunostimulant effect. The isolation of polysaccharide from Noni fruit has been optimized according to four different methods based on macrophage and lymphocyte activities. We found the highest polysaccharide content from one of the four methods isolation. A method of polysaccharide isolation which has the highest immunostimulant effect was used for further observation as co-chemotherapy. The aim of the study: was to evaluate the isolated polysaccharide from the method of choice as co-chemotherapy of doxorubicin for the growth of Vero, He-La, and T47D cell lines in vitro. The method: in vitro growth assay of Vero, He-La, and T47D cell lines was done using MTT-reduction method, and apoptosis test was done by double staining method to evaluate the induction apoptotic effect of the combination. Every group was treated with doxorubicin and isolated polysaccharide from method of choice with 4 variances of concentrations (25 µg/ml, 50 µg/ml, 100 µg/ml and 200 µg/ml) a long with negative control (doxorubicin only) and normal control (without doxorubicin or polysaccharide administration). Results: The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin against He-La and T47D cell lines influenced the highest cytotoxic effect by suppressing cell viability comparing with doxorubicin only. The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin-induced apoptotic effect the He-La cell line comparing with doxorubicin only. The result of the study: it can be concluded that the combination of polysaccharide fraction and doxorubicin effect more selective toward He-La and T47D cell lines than to Vero cell line. It can be suggested isolated polysaccharide from the method of choice has co-chemotherapy activity against doxorubicin.

Keywords: polysaccharide, noni fruit, doxorubicin, cancer cell lines, vero cell line

Procedia PDF Downloads 223
5698 Antioxidant and Cytotoxic Effects of Different Extracts of Fruit Peels Against Three Cancer Cell Lines

Authors: Emad A. Shalaby

Abstract:

Cancer is a disease that causes abnormal cell proliferation and invades nearby tissues. Lung cancer is the second most frequent cancer worldwide. Natural anti-cancer drugs have been developed with low side effects and toxicity. Citrus peels and extracts have been demonstrated to have significant pharmacological and physiological effects as a result of the high concentration of phenolic compounds found in citrus fruits, particularly peels. Tangerine peels can serve as an effective source of bioactive substances such as phenolics, flavonoids, and catechins, which have antioxidant, antibacterial, anticancer, and anti-inflammatory properties. Consequently, this work aims to determine the anticancer activity of ethanol extract of Tangerine peels against the A549 cell line and identify the phenolic compound profile (19 compounds) by using HPLC. Anticancer and antioxidant potentials of the extract were evaluated by MTT assay and TLC- TLC-bioautography sprayed with DPPH reagent, respectively. The obtained results revealed that tangerine peel extract showed significant activity against the A549 cell line with IC50 of 97.66 μg/mL. HPLC analysis proved that the highest concentration is naringenin 464.05 mg/g. More studies indicate that naringenin has significant anticancer potential on A549 cancer cells. The results showed that naringenin binds t0 EGFR protein in A549 with high binding affinity and thus may reduce lung cancer cell migration and enhance the apoptosis of cancer cells. From the obtained results it could be concluded that tangerine peel extract is an effective anti-cancer agent that may potentially serve as a natural therapeutic option for lung cancer treatment.

Keywords: tangerine peel, A549 cell line, anticancer, naringenin, HPLC analysis, naringenin, TLC bioautography

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5697 Early Diagnosis and Treatment of Cancer Using Synthetic Cationic Peptide

Authors: D. J. Kalita

Abstract:

Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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5696 Recovery through Shattered Life: The Life World of Illness after Being Diagnosed with Breast Cancer in Taiwan

Authors: Min-Tao Hsu

Abstract:

This study aims to explore the lived experiences of women with breast cancer, including their life world of illness and their adaptation to breast cancer. Breast cancer is not only a potentially lethal disease, but also a disease that may lead to many irreversible changes for female patients. Especially, in a culture where the wholeness is pursuit as an essential value, the sickness and/or broken body bring great challenge of life. Based on holism and symbolic interactionism, this study used interpretive ethnography including in-depth interviews and participant observations to collect the narrative of women with breast cancer concerning their illness experience. In addition, this study used Agar’s hermeneutic cycle to analyze data. The average age of 35 participants was 54.2. A total of 15 patients were within 2 years of onset, 5 patients were within 2-5 years of the treatment observation period, and 15 patients suffered from breast cancer for more than 5 years. The average age of onset was 50.4. Result: The main storyline of the life world of illness is ‘breast cancer is a turning point of life.’ Loss of breast was in terms of ‘no more a woman’ in Taiwanese culture. Two young women, one in her newly wedded and another right before marry, were divorced and cancelled wedding right after being diagnosed. All of them addressed that they have a ‘broken body.’ Single women accounted that they won’t marry for not being humiliated and most of married women said they never show female body in front of her husband or partner even in intimacy encounter. Three common themes were discovered: 1) new self and new identity; 2) new social relationships and new me; 3) new body and new life. The intertwining bodies, illness, selves, suffering, and medical treatments of female patients were observed. More, the recovery, of cause, was happened when new self, relationship, and new body were generated. Their identity to be a woman and a wife is shattered and their life is urged into another facet. For helping them to recovery from such situation, building a new identity and new social fabric on the new body need to be included in nursing care plan.

Keywords: breast cancer, illness narrative, world of illness, self-healing, interpretive ethnography

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5695 Contribution of PALB2 and BLM Mutations to Familial Breast Cancer Risk in BRCA1/2 Negative South African Breast Cancer Patients Detected Using High-Resolution Melting Analysis

Authors: N. C. van der Merwe, J. Oosthuizen, M. F. Makhetha, J. Adams, B. K. Dajee, S-R. Schneider

Abstract:

Women representing high-risk breast cancer families, who tested negative for pathogenic mutations in BRCA1 and BRCA2, are four times more likely to develop breast cancer compared to women in the general population. Sequencing of genes involved in genomic stability and DNA repair led to the identification of novel contributors to familial breast cancer risk. These include BLM and PALB2. Bloom's syndrome is a rare homozygous autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia and is associated with breast cancer when in a heterozygous state. PALB2, on the other hand, binds to BRCA2 and together, they partake actively in DNA damage repair. Archived DNA samples of 66 BRCA1/2 negative high-risk breast cancer patients were retrospectively selected based on the presence of an extensive family history of the disease ( > 3 affecteds per family). All coding regions and splice-site boundaries of both genes were screened using High-Resolution Melting Analysis. Samples exhibiting variation were bi-directionally automated Sanger sequenced. The clinical significance of each variant was assessed using various in silico and splice site prediction algorithms. Comprehensive screening identified a total of 11 BLM and 26 PALB2 variants. The variants detected ranged from global to rare and included three novel mutations. Three BLM and two PALB2 likely pathogenic mutations were identified that could account for the disease in these extensive breast cancer families in the absence of BRCA mutations (BLM c.11T > A, p.V4D; BLM c.2603C > T, p.P868L; BLM c.3961G > A, p.V1321I; PALB2 c.421C > T, p.Gln141Ter; PALB2 c.508A > T, p.Arg170Ter). Conclusion: The study confirmed the contribution of pathogenic mutations in BLM and PALB2 to the familial breast cancer burden in South Africa. It explained the presence of the disease in 7.5% of the BRCA1/2 negative families with an extensive family history of breast cancer. Segregation analysis will be performed to confirm the clinical impact of these mutations for each of these families. These results justify the inclusion of both these genes in a comprehensive breast and ovarian next generation sequencing cancer panel and should be screened simultaneously with BRCA1 and BRCA2 as it might explain a significant percentage of familial breast and ovarian cancer in South Africa.

Keywords: Bloom Syndrome, familial breast cancer, PALB2, South Africa

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5694 Discovery, Design and Synthesis of Some Novel Antitumor 1,2,4-Triazine Derivatives as C-Met Kinase Inhibitors

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

Abstract:

The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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5693 Psychosocial Determinants of Quality of Life After Treatment for Breast Cancer - A Systematic Review

Authors: Lakmali Anthony, Madeline Gillies

Abstract:

Purpose: Decreasing mortality has led to increased focus on patient-reported outcomes such as quality of life (QoL) in breast cancer. Breast cancer patients often have decreased QoL even after treatment is complete. This systematic review of the literature aims to identify psychosocial factors associated with decreased QoL in post-treatment breast cancer patients. Methodology: This systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search was conducted in MEDLINE, EMBASE, and PsychINFO using MeSH headings. The two authors screened studies for relevance and extracted data. Results: Seventeen studies were identified, including 3,150 total participants (mean = 197) with a mean age of 51.9 years. There was substantial heterogeneity in measures of QoL. The most common was the European Organisation for Research and Treatment of Cancer QLQ-C30 (n=7, 41.1%). Most studies (n=12, 70.5%) found that emotional distress correlated with poor QoL, while 3 found no significant association. The most common measure of emotional distress was the Hospital Anxiety and Depression Scale (n=12, 70.5%). Other psychosocial factors associated with QoL were unmet needs, problematic social support, and negative affect. Clinicopathologic determinants included mastectomy without reconstruction, stage IV disease, and adjuvant chemotherapy. Conclusion: This systematic review provides a summary of the psychosocial determinants of poor QoL in post-treatment breast cancer patients, as well as the most commonly reported measures of these. An understanding of these potentially modifiable determinants of poor outcome is pivotal to the provision of quality, patient-centred care in surgical oncology.

Keywords: breast cancer, quality of life, psychosocial determinants, cancer surgery

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5692 Dynamic Contrast-Enhanced Breast MRI Examinations: Clinical Use and Technical Challenges

Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

Abstract:

Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

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5691 18 F-FDG PET/CT: Utility in Breast Cancer Surgery

Authors: R. Sonda, F. Pellini, A. Invento, S. Mirandola, F. Riolfatti, D. Grigolato, G. P. Pollini

Abstract:

The purpose of study is to assess utility of 18F-FDG PET/CT in patients with breast heteroplasia and possibility of changing the surgery/therapeutic treatment. Among these "under fourty-five" candidated for NAC, the prevalence of change in therapeutic approach in comparison with first and second level exams has been: 43.75%, while by 22% among the "over forty-five". The surgical timing according to first-level exams have been deferred in 31.46% cases; PET/CT has led to a change in therapeutic treatment of 48.31% on the previous given; then the addition of MRI has led to a similar variation. For all the total patients, the prevalent choice was found to the debulking approach by increasing from a prevalence of 12.92% to 15.17%, resulting in a reduction of conservative one.The present study set itself the objective to demonstrate how the FDG PET/CT could improve on breast imaging according to a more appropriate surgery.

Keywords: breast cancer, FGD PET/CT, preoperative staging, surgical approach

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5690 Hyper Tuned RBF SVM: Approach for the Prediction of the Breast Cancer

Authors: Surita Maini, Sanjay Dhanka

Abstract:

Machine learning (ML) involves developing algorithms and statistical models that enable computers to learn and make predictions or decisions based on data without being explicitly programmed. Because of its unlimited abilities ML is gaining popularity in medical sectors; Medical Imaging, Electronic Health Records, Genomic Data Analysis, Wearable Devices, Disease Outbreak Prediction, Disease Diagnosis, etc. In the last few decades, many researchers have tried to diagnose Breast Cancer (BC) using ML, because early detection of any disease can save millions of lives. Working in this direction, the authors have proposed a hybrid ML technique RBF SVM, to predict the BC in earlier the stage. The proposed method is implemented on the Breast Cancer UCI ML dataset with 569 instances and 32 attributes. The authors recorded performance metrics of the proposed model i.e., Accuracy 98.24%, Sensitivity 98.67%, Specificity 97.43%, F1 Score 98.67%, Precision 98.67%, and run time 0.044769 seconds. The proposed method is validated by K-Fold cross-validation.

Keywords: breast cancer, support vector classifier, machine learning, hyper parameter tunning

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5689 Multiple-Channel Coulter Counter for Cell Sizing and Enumeration

Authors: Yu Chen, Seong-Jin Kim, Jaehoon Chung

Abstract:

High throughput cells counting and sizing are often required for biomedical applications. Here we report design, fabrication and validating of a micro-machined Coulter counter device with multiple-channel to realize such application for low cost. Multiple vertical through-holes were fabricated on a silicon chip, combined with the PDMS micro-fluidics channel that serves as the sensing channel. In order to avoid the crosstalk introduced by the electrical connection, instead of measuring the current passing through, the potential of each channel is monitored, thus the high throughput is possible. A peak of the output potential can be captured when the cell/particle is passing through the microhole. The device was validated by counting and sizing the polystyrene beads with diameter of 6 μm, 10 μm and 15 μm. With the sampling frequency to be set at 100 kHz, up to 5000 counts/sec for each channel can be realized. The counting and enumeration of MCF7 cancer cells are also demonstrated.

Keywords: Coulter counter, cell enumeration, high through-put, cell sizing

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5688 Developing an Accurate AI Algorithm for Histopathologic Cancer Detection

Authors: Leah Ning

Abstract:

This paper discusses the development of a machine learning algorithm that accurately detects metastatic breast cancer (cancer has spread elsewhere from its origin part) in selected images that come from pathology scans of lymph node sections. Being able to develop an accurate artificial intelligence (AI) algorithm would help significantly in breast cancer diagnosis since manual examination of lymph node scans is both tedious and oftentimes highly subjective. The usage of AI in the diagnosis process provides a much more straightforward, reliable, and efficient method for medical professionals and would enable faster diagnosis and, therefore, more immediate treatment. The overall approach used was to train a convolution neural network (CNN) based on a set of pathology scan data and use the trained model to binarily classify if a new scan were benign or malignant, outputting a 0 or a 1, respectively. The final model’s prediction accuracy is very high, with 100% for the train set and over 70% for the test set. Being able to have such high accuracy using an AI model is monumental in regard to medical pathology and cancer detection. Having AI as a new tool capable of quick detection will significantly help medical professionals and patients suffering from cancer.

Keywords: breast cancer detection, AI, machine learning, algorithm

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5687 Developing a Health Literacy Questionnaire in Breast Cancer

Authors: Lida Moghaddam-Banaem, Mahmood Tavoosi, Soheila Khalili

Abstract:

Objective: The main objective of this study was designing a breast cancer health literacy questionnaire and assess its psychometric properties. Methods: A comprehensive literature review was performed to develop a primary questionnaire consisting of five domains. Qualitative and quantitative content validity were assessed by relevant experts, and after some modifications, the content validity index (CVI) and content validity ratio (CVR) were calculated. Qualitative and quantitative face validity were evaluated by a number of patients, and the impact score for each item was calculated. 225 women with breast cancer were asked to fill out the questionnaire and construct validity was determined by using exploratory factor analysis. The reliability was tested by Cronbach's alpha coefficient. Results: A 36-item questionnaire with five domains of reading, having access, understanding, assessing/judgment, and decision making/behavior was designed. 2 items were omitted in the qualitative content validity process. All items achieved optimum values in CVI, CVR and impact scores. Content and face validity of the questionnaire were confirmed too. According to the exploratory factor analysis, the five-factor solution accounted for 64.98 percent of the observed variance. Conclusion: Due to the obtained satisfactory validity and reliability, this tool can be used to assess health literacy in women with breast cancer. Health policy makers can use these findings for improving health-related behaviors in breast cancer patients.

Keywords: health literacy, breast cancer, questionnaire, psychometric properties

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5686 Microwave Tomography: The Analytical Treatment for Detecting Malignant Tumor Inside Human Body

Authors: Muhammad Hassan Khalil, Xu Jiadong

Abstract:

Early detection through screening is the best tool short of a perfect treatment against the malignant tumor inside the breast of a woman. By detecting cancer in its early stages, it can be recognized and treated before it has the opportunity to spread and change into potentially dangerous. Microwave tomography is a new imaging method based on contrast in dielectric properties of materials. The mathematical theory of microwave tomography involves solving an inverse problem for Maxwell’s equations. In this paper, we present designed antenna for breast cancer detection, which will use in microwave tomography configuration.

Keywords: microwave imaging, inverse scattering, breast cancer, malignant tumor detection

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5685 Microfluidic Based High Throughput Screening System for Photodynamic Therapy against Cancer Cells

Authors: Rina Lee, Chung-Hun Oh, Eunjin Lee, Jeongyun Kim

Abstract:

The Photodynamic therapy (PDT) is a treatment that uses a photosensitizer as a drug to damage and kill cancer cells. After injecting the photosensitizer into the bloodstream, the drug is absorbed by cancer cells selectively. Then the area to be treated is exposed to specific wavelengths of light and the photosensitizer produces a form of oxygen that kills nearby cancer cells. PDT is has an advantage to destroy the tumor with minimized side-effects on normal cells. But, PDT is not a completed method for cancer therapy. Because the mechanism of PDT is quite clear yet and the parameters such as intensity of light and dose of photosensitizer are not optimized for different types of cancers. To optimize these parameters, we suggest a novel microfluidic system to automatically control intensity of light exposure with a personal computer (PC). A polydimethylsiloxane (PDMS) microfluidic chip is composed with (1) a cell culture channels layer where cancer cells were trapped to be tested with various dosed photofrin (1μg/ml used for the test) as the photosensitizer and (2) a color dye layer as a neutral density (ND) filter to reduce intensity of light which exposes the cell culture channels filled with cancer cells. Eight different intensity of light (10%, 20%, …, 100%) are generated through various concentrations of blue dye filling the ND filter. As a light source, a light emitting diode (LED) with 635nm wavelength was placed above the developed PDMS microfluidic chip. The total time for light exposure was 30 minutes and HeLa and PC3 cell lines of cancer cells were tested. The cell viability of cells was evaluated with a Live/Dead assay kit (L-3224, Invitrogen, USA). The stronger intensity of light exposed, the lower viability of the cell was observed, and vice versa. Therefore, this system was demonstrated through investigating the PDT against cancer cell to optimize the parameters as critical light intensity and dose of photosensitizer. Our results suggest that the system can be used for optimizing the combinational parameters of light intensity and photosensitizer dose against diverse cancer cell types.

Keywords: photodynamic therapy, photofrin, high throughput screening, hela

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5684 Prognostic Significance of Nuclear factor kappa B (p65) among Breast Cancer Patients in Cape Coast Teaching Hospital

Authors: Precious Barnes, Abraham Mensah, Leonard Derkyi-Kwarteng, Benjamin Amoani, George Adjei, Ernest Adankwah, Faustina Pappoe, Kwabena Dankwah, Daniel Amoako-Sakyi, Samuel Victor Nuvor, Dorcas Obiri-Yeboah, Ewura Seidu Yahaya, Patrick Kafui Akakpo, Roland Osei Saahene

Abstract:

Context: Breast cancer is a prevalent and aggressive type of cancer among African women, with high mortality rates in Ghana. Nuclear factor kappa B (NF-kB) is a transcription factor that has been associated with tumor progression in breast cancer. However, there is a lack of published data on NF-kB in breast cancer patients in Ghana or other African countries. Research Aim: The aim of this study was to assess the prognostic significance of NF-kB (p65) expression and its association with various clinicopathological features in breast cancer patients at the Cape Coast Teaching Hospital in Ghana. Methodology: A total of 90 formalin-fixed breast cancer tissues and 15 normal breast tissues were used in this study. The expression level of NF-kB (p65) was examined using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Findings: The study found that NF-kB (p65) was expressed in 86.7% of breast cancer tissues. There was a significant relationship between NF-kB (p65) expression and tumor grade, proliferation index (Ki67), and molecular subtype. High-level expression of NF-kB (p65) was more common in tumor grade 3 compared to grade 1, and Ki67 > 20 had higher expression of NF-kB (p65) compared to Ki67 ≤ 20. Triple-negative breast cancer patients had the highest overexpression of NF-kB (p65) compared to other molecular subtypes. There was no significant association between NF-kB (p65) expression and other clinicopathological parameters. Theoretical Importance: This study provides important insights into the expression of NF-kB (p65) in breast cancer patients in Ghana, particularly in relation to tumor grade and proliferation index. The findings suggest that NF-kB (p65) could serve as a potential biological marker for cancer stage, progression, prognosis and as a therapeutic target. Data Collection and Analysis Procedures: Formalin-fixed breast cancer tissues and normal breast tissues were collected and analyzed using immunohistochemical techniques. Correlation analysis between NF-kB (p65) expression and clinicopathological features was performed using SPSS version 25. Question Addressed: This study addressed the question of the prognostic significance of NF-kB (p65) expression and its association with clinicopathological features in breast cancer patients in Ghana. Conclusion: This study, the first of its kind in Ghana, demonstrates that NF-kB (p65) is highly expressed among breast cancer patients at the Cape Coast Teaching Hospital, especially in triple-negative breast cancer patients. The expression of NF-kB (p65) is associated with tumor grade and proliferation index. NF-kB (p65) could potentially serve as a biological marker for cancer stage, progression, prognosis, and as a therapeutic target.

Keywords: breast cancer, Ki67, NF-kB (p65), tumor grade

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5683 Experiencing Scarred Body among Thai Women Living with Breast Cancer

Authors: Dusanee Suwankhong, Pranee Liamputtong

Abstract:

Breast surgery leaves undesirable scars to all women who experienced mastectomy, despite the fact that this could be a principle approach to save one life. This paper explores how Thai women living with breast cancer perceived and experienced a scarred body after breast surgery. In-depth interviews and drawing methods were employed among 20 women diagnosed with breast cancer. The interviewed data were analysed using thematic analysis method. The results showed that all women with breast cancer who underwent breast surgery perceived and experienced scar as a persisting and visible side-effect. This disfigurement appearance presented a negative image of feminine identity and led to emotional burdens among women. They responded to being scarred in different ways relating to their perceptions of body and changes. The older group had less embarrassed feelings towards being scarred comparing to the younger one. All women tried to seek means to cope with such physical impairment and keep balance life related to their condition. For example, they relied on Buddhism practice and tried to heal the keloid using natural products. Scars appeared to be an unpleasant effect for women who underwent breast mastectomy. Nurses and health care professionals in the local health service sectors need to pay close attention to how the women see the scarred body and their experiences of living with the distorted feminine appearance, and to provide sensitive support that meets the needs of these vulnerable women. The suitable supports can reduce the sense of embarrassment and increase their sense of self-confidence about their social femininity.

Keywords: breast surgery, emotional response, qualitative study, scars, Thai women

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5682 Investigation p53 Codon 72 Polymorphism and miR-146a rs2910164 Polymorphism in Breast Cancer

Authors: Marjan Moradi Fard, Hossein Rassi, Masoud Houshmand

Abstract:

Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism, genotypes

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5681 Computer Aided Analysis of Breast Based Diagnostic Problems from Mammograms Using Image Processing and Deep Learning Methods

Authors: Ali Berkan Ural

Abstract:

This paper presents the analysis, evaluation, and pre-diagnosis of early stage breast based diagnostic problems (breast cancer, nodulesorlumps) by Computer Aided Diagnosing (CAD) system from mammogram radiological images. According to the statistics, the time factor is crucial to discover the disease in the patient (especially in women) as possible as early and fast. In the study, a new algorithm is developed using advanced image processing and deep learning method to detect and classify the problem at earlystagewithmoreaccuracy. This system first works with image processing methods (Image acquisition, Noiseremoval, Region Growing Segmentation, Morphological Operations, Breast BorderExtraction, Advanced Segmentation, ObtainingRegion Of Interests (ROIs), etc.) and segments the area of interest of the breast and then analyzes these partly obtained area for cancer detection/lumps in order to diagnosis the disease. After segmentation, with using the Spectrogramimages, 5 different deep learning based methods (specified Convolutional Neural Network (CNN) basedAlexNet, ResNet50, VGG16, DenseNet, Xception) are applied to classify the breast based problems.

Keywords: computer aided diagnosis, breast cancer, region growing, segmentation, deep learning

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5680 The Effectiveness of Laughing Qigong for Women with Breast Cancer in Community

Authors: Chueh Chang, Chia-jung Hsieh, Fu-yu Yu, Yu-Hwa Lin

Abstract:

Background:The majority of women diagnosed with breast cancer undergo treatment involving surgery and radiotherapy or chemotherapy, or both. With these major advances in breast cancer management, many patients still have to deal with short or long-term side effects and psychological distress related to the disease and treatment, which have a substantial impact on their quality of life. The Laughing Qigong Program (LQP) is an interactive laughter program that combines the physical and physiological benefits of laughter with the mental benefits of Chinese qigong. Purpose: In order to improve the quality of life for breast cancer women in the community as well as echoing the WHO 2004 “Promoting Mental Health” for every one. This study focused on how to promote the positive mental health for women of breast cancer through the “laughter program” in Taiwan. During the presentation, how to practice Laughing Qigong will be demonstrated. Method: Using nonequivalent pretest-posttest design, ix-one breast cancer patients were volunteered to enroll in this study from the Taiwan Breast Cancer Alliance (TBCA). Thirty patients were assigned to the experimental group and the other 31 patients were assigned to the control group. The women who were assigned to the experimental group received laughter program one hour per session, once a week, totally 12 sessions. All subjects were tested before and after the intervention on the following: Self-Esteem scale (RSE), Face Scale (FS), Anxiety and pain experience were measured as psychological markers; saliva cortisol (CS) as an immunological marker; blood pressure (BP), heart rate (HR),and heart rate variability (HRV) as physiological markers of the body’s response to stress. Results: After comparing the experimental and control groups, the results revealed that those breast cancer women with “laughing program” their sense of humor were improved, less uncomfortable on self report physical conditions, more positive attitudes toward stress management by using laughter, and had emotional improvement according to the face scale.

Keywords: mental health promotion, breast cancer, laughing Qigong, women

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5679 Fam111b Gene Dysregulation Contributes to the Malignancy in Fibrosarcoma, Poor Clinical Outcomes in Poiktmp and a Low-cost Method for Its Mutation Screening

Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

Abstract:

Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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5678 Nurse’s Role in Early Detection of Breast Cancer through Mammography and Genetic Screening and Its Impact on Patient's Outcome

Authors: Salwa Hagag Abdelaziz, Dorria Salem, Hoda Zaki, Suzan Atteya

Abstract:

Early detection of breast cancer saves many thousands of lives each year via application of mammography and genetic screening and many more lives could be saved if nurses are involved in breast care screening practices. So, the aim of the study was to identify nurse's role in early detection of breast cancer through mammography and genetic screening and its impact on patient's outcome. In order to achieve this aim, 400 women above 40 years, asymptomatic were recruited for mammography and genetic screening. In addition, 50 nurses and 6 technologists were involved in the study. A descriptive analytical design was used. Five tools were utilized: sociodemographic, mammographic examination and risk factors, women's before, during and after mammography, items relaying to technologists, and items related to nurses were also obtained. The study finding revealed that 3% of women detected for malignancy and 7.25% for fibroadenoma. Statistically, significant differences were found between mammography results and age, family history, genetic screening, exposure to smoke, and using contraceptive pills. Nurses have insufficient knowledge about screening tests. Based on these findings the present study recommended involvement of nurses in breast care which is very important to in force population about screening practices.

Keywords: mammography, early detection, genetic screening, breast cancer

Procedia PDF Downloads 533
5677 Reliability of Social Support Measurement Modification of the BC-SSAS among Women with Breast Cancer Who Undergone Chemotherapy in Selected Hospital, Central Java, Indonesia

Authors: R. R. Dewi Rahmawaty Aktyani Putri, Earmporn Thongkrajai, Dedy Purwito

Abstract:

There were many instruments have been developed to assess social support which has the different dimension in breast cancer patients. The Issue of measurement is a challenge to determining the component of dimensional concept, defining the unit of measurement, and establishing the validity and reliability of the measurement. However, the instruments where need to know how much support which obtained and perceived among women with breast cancer who undergone chemotherapy which it can help nurses to prevent of non-adherence in chemotherapy. This study aimed to measure the reliability of BC-SSAS instrument among 30 Indonesian women with breast cancer aged 18 years and above who undergone chemotherapy for six cycles in the oncological unit of Outpatient Department (OPD), Margono Soekardjo Hospital, Central Java, Indonesia. Data were collected during October to December 2015 by using modified the Breast Cancer Social Support Assessment (BC-SSAS). The Cronbach’s alpha analysis was carried out to measure internal consistency for reliability test of BC-SSAS instrument. This study used five experts for content validity index. The results showed that for content validity, I-CVI was 0.98 and S-CVI was 0.98; Cronbach’s alpha value was 0.971 and the Cronbach’s alpha coefficients for the subscales were high, with 0.903 for emotional support, 0.865 for informational support, 0.901 for tangible support, 0.897 for appraisal support and 0.884 for positive interaction support. The results confirmed that the BC-SSAS instrument has high reliability. BC-SSAS instruments were reliable and can be used in health care services to measure the social support received and perceived among women with breast cancer who undergone chemotherapy so that preventive interventions can be developed and the quality of health services can be improved.

Keywords: BC-SSAS, women with breast cancer, chemotherapy, Indonesia

Procedia PDF Downloads 341
5676 Evaluation of Promoter Hypermethylation in Tissue and Blood of Non-Small Cell Lung Cancer Patients and Association with Survival

Authors: Ashraf Ali, Kriti Upadhyay, Puja Sohal, Anant Mohan, Randeep Guleria

Abstract:

Background: Gene silencing by aberrant promoter hypermethylation is common in lung cancer and is an initiating event in its development. Aim: To evaluate the gene promoter hypermethylation frequency in serum and tissue of lung cancer patients. Method: 95 newly diagnosed untreated advance stage lung cancer patients and 50 cancer free matched controls were studied. Bisulfite modification of tissue and serum DNA was done; modified DNA was used as a template for methylation-specific PCR analysis. Survival was assessed for one year. Results: Of 95 patients, 82% were non-small cell lung cancer (34% squamous cell carcinoma, 34% non-small cell lung cancer and 14% adenocarcinoma) and 18% were small cell lung cancer. Biopsy revealed that tissue of 89% and 75% of lung cancer patients and 85% and 52% of controls had promoter hypermethylated for MGMT (p=0.35) and p16(p<0.001) gene, respectively. In serum, 33% and 49% of lung cancer patients and 28% and 43% controls were positive for MGMT and p16 gene. No significant correlation was found between survival and clinico-pathological parameters. Conclusion: High gene promoter methylation frequency of p16 gene in tissue biopsy may be linked with early stages of carcinogenesis. Appropriate follow-up is required for confirmation of this finding.

Keywords: lung cancer, MS- PCR, methylation, molecular biology

Procedia PDF Downloads 163
5675 The Implication of Small Group Therapy on Sexuality in Breast Cancer Survivors

Authors: Cherng-Jye Jeng, Ming-Feng Hou, Hsing-Yuan Liu, Chuan-Feng Chang, Lih-Rong Wang, Yen-Chin Lin

Abstract:

Introduction: The incidence of breast cancer has gradually increased in Taiwan, and the characteristic of younger ages impact these women in their middle age, and may also cause challenges in terms of family, work, and illness. Breasts are symbols of femininity, as well as of sex. For women, breasts are important organs for the female identity and sexual expression. Losing breasts not only affects the female role, but would also affect sexual attraction and sexual desire. Thus, women with breast cancer who have need for mastectomies experience physical incompletion, which affects women’s self-confidence, physical image, and self-orientation. Purposes: 1. To understand the physical experience of women with breast cancer. 2. To explore the issue of sexual issues on the health effects of women with breast cancer. 3. To construct a domestic sex life issue group model for domestic women with breast cancer. 4. To explore the accompaniment experiences and sexual relationship adjustments of spouses when women have breast cancer. Method: After the research plan passes IRB review, participants will be recruited at breast surgery clinic in the affiliated hospital, to screen suitable subjects for entry into the group. Between March and May 2015, two sexual health and sex life consultation groups were conducted, which were (1) 10 in postoperative groups for women with cancer; (2) 4 married couples group for postoperative women with cancer. After sharing experiences and dialogue, women can achieve mutual support and growth. Data organization and analysis underwent descriptive analysis in qualitative research, and the group process was transcribed into transcripts for overall-content and category-content analysis. Results: Ten women with breast cancer believed that participating in group can help them exchange experiences, and elevate sexual health. The main issues include: (1) after breast cancer surgery, patients generally received chemotherapy or estrogen suppressants, causing early menopause; in particular, vaginal dryness can cause pain or bleeding in intercourse, reducing their desire for sexual activity; (2) breast cancer accentuates original spousal or family and friend relationships; some people have support and care from their family, and spouses emphasize health over the appearance of breasts; however, some people do not have acceptance and support from their family, and some even hear spousal sarcasm about loss of breasts; (3) women with breast cancer have polarized expressions of optimism and pessimism in regards to their emotions, beliefs, and body image regarding cancer; this is related to the women’s original personalities, attribution of causes of cancer, and extent of worry about relapse. Conclusion: The research results can be provided as a reference to medical institutions or breast cancer volunteer teams, to pay attention to maintaining the health of women with breast cancer.

Keywords: women with breast cancer, experiences of objectifying the body, quality of sex life, sexual health

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5674 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer

Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

Abstract:

Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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