Search results for: breast
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 644

Search results for: breast

434 Effect of Acceptance and Commitment Therapy in Cognitive Function among Breast Cancer Patients in Eastern Country

Authors: Arunima Datta, Prathama Guha Chaudhuri, Ashis Mukhopadhyay

Abstract:

Background: Acceptance and commitment therapy (ACT) is one of the newer forms (third wave) therapy. This therapy helps a cancer patient to increase acceptance level about their disease as well as their present situation. Breast cancer patients are known to suffer from depression and mild cognitive impairment; both affect their quality of life. Objectives:The present study had assessed effect of structured ACT intervention on cognitive function and acceptance level among breast cancer patients who were undergoing chemotherapy. Method: Data was collected from 123 breast cancer patients those who were undergoing chemotherapy were willing to undergo psychological treatment, with no history of past psychiatric illness. Their baseline of cognitive function and acceptance levels were assessed using validated tools. The effect of sociodemographic factors and clinical factors on cognitive function was determined at baseline.The participants were randomly divided into two groups: experimental (ACT, 4 sessions over 2 months) and control group. Cognitive function and acceptance level were measured during post intervention on 2months follow-up. Appropriate statistical analyses were performed to determine the effect on cognitive function and acceptance level in two groups. Result: At baseline, the factors that significantly influenced slower speed of task performance were ER PR HER2 status; number of chemo cycle, treatment type (Adjuvant and neo-adjuvant) was related with that. Sociodemographic characteristics did not show any significant difference between slow and fast performance. Per and post intervention analysis showed that ACT intervention resulted in significant difference both in terms of speed of cognitive performance and acceptance level. Conclusion: ACT is an effective therapeutic option for treating mild cognitive impairment and improve acceptance level among breast cancer patients undergoing chemotherapy.

Keywords: acceptance and commitment therapy, breast cancer, quality of life, cognitive function

Procedia PDF Downloads 276
433 Periareolar Zigzag Incision in the Conservative Surgical Treatment of Breast Cancer

Authors: Beom-Seok Ko, Yoo-Seok Kim, Woo-Sung Lim, Ku-Sang Kim, Hyun-Ah Kim, Jin-Sun Lee, An-Bok Lee, Jin-Gu Bong, Tae-Hyun Kim, Sei-Hyun Ahn

Abstract:

Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. It is safe therapeutic procedure in early breast cancers, because it provides the same level of overall survival as mastectomy. There are a number of different types of incisions used to BCS. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. Periareolar incision is often used when the small tumor relatively close to the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. In plastic surgery, various methods such as zigzag incisions have been recommended to achieve satisfactory esthetic results. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the oncological safety of procedures by studying the status of the surgical margins of the excised tumor specimen and reduces the need for further surgery. Methods: Between January 2016 and September 2016, 148 women with breast cancer underwent BCS or mastectomy by the same surgeon in ASAN medical center. Patients with exclusion criteria were excluded from this study if they had a bilateral breast cancer or underwent resection of the other tumors or taken axillary dissection or performed other incision methods. Periareolar zigzag incision was performed and excision margins of the specimen were identified frozen sections and paraffin-embedded or permanent sections in all patients in this study. We retrospectively analyzed tumor characteristics, the operative time, size of specimen, the distance from the tumor to nipple. Results: A total of 148 patients were reviewed, 72 included in the final analysis, 76 excluded. The mean age of the patients was 52.6 (range 25-19 years), median tumor size was 1.6 cm (range, 0.2-8.8), median tumor distance from the nipple was 4.0 cm (range, 1.0-9.0), median excised specimen sized was 5.1 cm (range, 2.8-15.0), median operation time was 70.0 minute (range, 39-138). All patients were discharged with no sign of infection or skin necrosis. Free resection margin was confirmed by frozen biopsy and permanent biopsy in all samples. There were no patients underwent reoperation. Conclusions: We suggest that periareolar zigzag incision can provide a good surgical field to remove a relatively large tumor and may provide cosmetically good outcomes.

Keywords: periareolar zigzag incision, breast conserving surgery, breast cancer, resection margin

Procedia PDF Downloads 201
432 Cytotoxic Activity of Acetone and Ethanol Overripe Tempe Extracts against MCF-7 Breast Cancer Cells and Their Antioxidant Property

Authors: Dian Muzdalifah, Anastasia F. Devi, Zatil A. Athaillah, Linar Z. Udin

Abstract:

Tempe is a functional food prepared from soybeans through Rhizopus spp fermentation. It is well known as functional food, originated from Indonesia. Most studies on tempe functionalities refer to ripe (48 h fermentation) tempe and only limited studies discuss overripe tempe while longer fermentation time possibly increased tempe health benefit. Hence, the present study was performed to investigate the cytotoxic activity againts MCF-7 breast cancer cells and antioxidant property of tempe prepared from 0–156 h of fermentation. Tempe samples were dried and extracted with acetone and ethanol, respectively. Their extracts were used for subsequent analysis. The cytotoxic activity was assessed on MCF 7 breast cancer cells using Alamar Blue method. The antioxidant activity was determined by DPPH free radical scavenging assay. The results indicated that acetone extracts of 108 h tempe had a potent cytotoxic activity against MCF-7 breast cancer cells (IC50 = 2.54 ± 0,30 μg/mL). Ethanol extracts of 108 h tempe also showed the potency, but at slightly higher IC50 (5.20 ± 1.01 μg/mL). Both acetone and ethanol extracts of 108 and 120 h tempe showed high antioxidant activity expressed as percent inhibition with no significant difference. However, acetone extracts of 120 h tempe (81.31 ± 3.70 %) had better ability to inhibit oxidation reaction than that of ethanol extracts (75.77 ± 6.00 %). It can be concluded that the cytotoxic activity of tempe from 0–156 h of fermentation is positively correlated to their corresponding antioxidant property. Longer fermentation time, up to 108 h, increased the ability of tempe to inhibit the growth of MCF-7 breast cancer cells and oxidative reaction. But extended fermentation time, up to 156 h, tends to decrease its ability. Further studies are encouraged to identify the active components contained in each extract.

Keywords: antioxidant property, cytotoxic activity, extracts, overripe tempeh

Procedia PDF Downloads 245
431 Phosphoinositide 3-Kinase-Dependent CREB Activation is Required for the Induction of Aromatase in Tamoxifen-Resistant Breast Cancer

Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

Abstract:

Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

Procedia PDF Downloads 382
430 Partition of Nonylphenol between Different Compartment for Mother-Fetus Pairs and Health Effects of Newborns

Authors: Chun-Hao Lai, Yu-Fang Huang, Pei-Wei Wang, Meng-Han Lin, Mei-Lien Chen

Abstract:

Nonylphenol (NP) is a degradation product of nonylphenol ethoxylates (NPEOs). It is a well-known endocrine disruptor which may cause estrogenic effects. The growing fetus and infants are more vulnerable to exposure to NP than adults. It is important to know the levels and influences of prenatal exposure to NP. The aims of this study were (1) to determine the levels of prenatal exposure among Taiwanese, (2) to evaluate the potential risk for the infants who were breastfed and exposed to NP through the milk. (3) To investigate the correlation between birth outcomes and prenatal exposure to NP. We analyzed thirty one pairs of maternal urines, placentas, first month’ breast milk by high-performance liquid chromatography coupling with fluorescence detector. The questionnaire included socio- demographics, lifestyle, delivery method, dietary and work history. Information about the birth outcomes were obtained from medical records. The daily intake of NP from breast milk was calculated using deterministic and probabilistic risk assessment methods. The geometric means and geometric standard deviation of NP levels in placenta, and breast milk in the first month were 31.2 (1.8) ng/g, 17.2 (1.6) ng/g, respectively. The medium of daily intake NP in breast milk was 1.33 μg/kg-bw/day in the first month. We found negative association between NP levels of placenta and birth height. And we observed negative correlation between maternal urine NP levels and birth weight. In this study, we could provide the NP exposure profile among Taiwan pregnant women and the daily intake of NP in Taiwan infants. Prenatal exposure to higher levels of NP may increase the risk of lower birth weight and shorter birth height.

Keywords: nonylphenol, mother, fetus, placenta, breast milk, urine

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429 2D and 3D Breast Cancer Cells Behave Differently to the Applied Free Palbociclib or the Palbociclib-Loaded Nanoparticles

Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

Abstract:

Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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428 Efficacy of Topical Ectoin Therapy for Acute Radiodermatitis Associated with Breast Cancer Radiotherapy: A Randomized Controlled Study

Authors: Nagwa E. Abd Elazim, Maha S. El-naggar, Rania H. Mohamed, Sara M. Awad

Abstract:

Background: Radiodermatitis is a common side effect of radiation therapy for breast cancer. However, there is no current consensus about effective standard therapy for the prevention and management of radiation dermatitis. Topical ectoine has demonstrated efficacy in the treatment of atopic dermatitis owing to its anti-inflammatory activity. Objective: To evaluate the efficacy of topical ectoine in comparison to traditional topical dexpanthenol treatment in the management of acute radiodermatitis in breast cancer patients undergoing adjuvant radiotherapy. Methods: Fifty patients were randomized to use either dexpanthenol 0.5% cream (25 patients), or ectoin 7% cream (25 patients), applied twice daily to the irradiated area during the radiation period and continued for 2 weeks after cessation of radiotherapy. Assessment of radiation skin toxicity using Common Terminology Criteria of Adverse Events (CTCAE) v4.0, radiation-associated symptoms, and adverse events were undertaken weekly during radiotherapy and 2 weeks after the end of radiotherapy. Results: Topical ectoine showed some clinical benefit over dexpanthenol, as shown by delayed time to onset (at week 3 versus week 2, respectively) and larger number of patients who reached grade 0 at the end of treatment (64% vs. 48%, respectively). The clinical symptoms of pain (p = 0.003) and itching (p = 0.001) attributable to radiation were less pronounced with ectoine than with dexpanthenol. Burning and hyperpigmentation were the most common side effects with ectoine. However, no significant difference between dexpanthenol and ectoine treatments was found in any of the side effects (p = 0.1). Conclusion: Ectoin was overall more effective in improving radiation dermatitis than topical dexpanthenol in breast cancer patients. Ectoin could be proposed as a preventive or curative treatment for patients undergoing postoperative irradiation for breast cancer. Further clinical studies with a larger number of patients are recommended for the confirmation of these preliminary results.

Keywords: breast cancer, dexapanthenol, ectoin, radiation dermatitis

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427 Exploring the Impact of Body Shape on Bra Fit: Integrating 3D Body Scanning and Traditional Patternmaking Methods

Authors: Yin-Ching Keung, Kit-Lun Yick

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The issue of bra fitting has persisted throughout history despite advancements in molded bra cups. To gain a deeper understanding of the interaction between the breast and bra pattern, this study combines the art of traditional bra patternmaking with 3D body scanning technology. By employing a 2D bra pattern drafting method and analyzing the effect of body shape on the desired bra cup shape, the study focuses on the differentiation of the lower cup among bras designed for flat and round body-shaped breasts. The results shed light on the impact of body shape on bra fit and provide valuable insights for further research and improvements in bra design, pattern drafting, and fit. The integration of 3D body scanning technology enhances the accuracy and precision of measurements, allowing for a more comprehensive analysis of the unique contours and dimensions of the breast and body. Ultimately, the study aims to provide individuals with different body shapes a more comfortable and well-fitted bra-wearing experience, contributing to the ongoing efforts to alleviate the longstanding problem of bra fitting.

Keywords: breast shapes, bra fitting, 3D body scanning, bra patternmaking

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426 Differences in Patient Satisfaction Observed between Female Japanese Breast Cancer Patients Who Receive Breast-Conserving Surgery or Total Mastectomy

Authors: Keiko Yamauchi, Motoyuki Nakao, Yoko Ishihara

Abstract:

The increase in the number of women with breast cancer in Japan has required hospitals to provide a higher quality of medicine so that patients are satisfied with the treatment they receive. However, patients’ satisfaction following breast cancer treatment has not been sufficiently studied. Hence, we investigated the factors influencing patient satisfaction following breast cancer treatment among Japanese women. These women underwent either breast-conserving surgery (BCS) (n = 380) or total mastectomy (TM) (n = 247). In March 2016, we conducted a cross-sectional internet survey of Japanese women with breast cancer in Japan. We assessed the following factors: socioeconomic status, cancer-related information, the role of medical decision-making, the degree of satisfaction regarding the treatments received, and the regret arising from the medical decision-making processes. We performed logistic regression analyses with the following dependent variables: extreme satisfaction with the treatments received, and regret regarding the medical decision-making process. For both types of surgery, the odds ratio (OR) of being extremely satisfied with the cancer treatment was significantly higher among patients who did not have any regrets compared to patients who had. Also, the OR tended to be higher among patients who chose to play a wanted role in the medical decision-making process, compared with patients who did not. In the BCS group, the OR of being extremely satisfied with the treatment was higher if, at diagnosis, the patient’s youngest child was older than 19 years, compared with patients with no children. The OR was also higher if patient considered the stage and characteristics of their cancer significant. The OR of being extremely satisfied with the treatments was lower among patients who were not employed on full-time basis, and among patients who considered the second medical opinions and medical expenses to be significant. These associations were not observed in the TM group. The OR of having regrets regarding the medical decision-making process was higher among patients who chose to play a role in the decision-making process as they preferred, and was also higher in patients who were employed on either a part-time or contractual basis. For both types of surgery, the OR was higher among patients who considered a second medical opinion to be significant. Regardless of surgical type, regret regarding the medical decision-making process decreases treatment satisfaction. Patients who received breast-conserving surgery were more likely to have regrets concerning the medical decision-making process if they could not play a role in the process as they preferred. In addition, factors associated with the satisfaction with treatment in BCS group but not TM group included the second medical opinion, medical expenses, employment status, and age of the youngest child at diagnosis.

Keywords: medical decision making, breast-conserving surgery, total mastectomy, Japanese

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425 A Cost-Evaluation Study on the Use of Negative Pressure Wound Therapy with Instillation for Salvage of Infected Implant-Based Breast Reconstructions

Authors: S. Haque, M. Kanapathy, E. Bollen, I. Younis, A. Mosahebi

Abstract:

Background: Implant loss due to infection is the most devastating complication of implant-based breast reconstruction. The use of negative pressure wound therapy with instillation (NPWTi) for salvage of infected implant-based breast reconstructions has shown promising results to allow early reinsertion of a new implant as an alternative to current management of delayed reinsertion. This study compares the cost implication of NPWTi against current management of delayed reinsertion of infected breast implants. Methods: 20 cases of an infected breast implant treated with NPWTi (V.A.C. VERAFLO™ Therapy) followed by early re-insertion of a new implant were compared with 20 cases who had delayed reinsertion (non-NPWTi). Average cost per person was calculated using total operative expenses, cost of inpatient stay, cost of investigations, cost of antibiotics, and cost of outpatient visits. Results: Treatment with NPWTi allowed for earlier re-insertion of a new implant (NPWTi: 9.04 ± 2.92 days vs. non-NPWTi: 236.25 ± 123.89 days). The average cost per patient for NPWTi and non-NPWTi was £14,343.13 ± £2,786.70 and £8,920.31 ± £3,005.73 respectively. All patients treated with NPWTi had one admission and spent 11.9 ± 4.1days as an inpatient while non-NPWTi patients had 2.1 ± 0.3 admissions with total length of inpatient stay of 7.1 ± 5.8days. Patients treated with NPWTi had more surgeries (NPWTi: 3.35 ± 0.81 vs. non-NPWTi: 2.2 ± 0.41), however 3 non-NPWTi cases required flap reconstruction. Patients treated with NPWTi had fewer total outpatient visits (NPWTi: 12 ± 6 vs. non-NPWTi: 14.2 ± 6.3). Conclusion: Patients treated with NPWTi incurred higher average cost per patient, longer inpatient stay, and more procedures; however, had early re-insertion of new implants and fewer admissions and outpatient visits. A further study on patient-reported outcome is essential to compare cost against patient benefit.

Keywords: breast reconstruction, cost evaluation, infection, negative pressure wound therapy

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

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

Abstract:

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

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

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423 Determination of Circulating Tumor Cells in Breast Cancer Patients by Electrochemical Biosensor

Authors: Gökçe Erdemir, İlhan Yaylım, Serap Erdem-Kuruca, Musa Mutlu Can

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It has been determined that the main reason for the death of cancer disease is caused by metastases rather than the primary tumor. The cells that leave the primary tumor and enter the circulation and cause metastasis in the secondary organs are called "circulating tumor cells" (CTCs). The presence and number of circulating tumor cells has been associated with poor prognosis in many major types of cancer, including breast, prostate, and colorectal cancer. It is thought that knowledge of circulating tumor cells, which are seen as the main cause of cancer-related deaths due to metastasis, plays a key role in the diagnosis and treatment of cancer. The fact that tissue biopsies used in cancer diagnosis and follow-up are an invasive method and are insufficient in understanding the risk of metastasis and the progression of the disease have led to new searches. Liquid biopsy tests performed with a small amount of blood sample taken from the patient for the detection of CTCs are easy and reliable, as well as allowing more than one sample to be taken over time to follow the prognosis. However, since these cells are found in very small amounts in the blood, it is very difficult to capture them and specially designed analytical techniques and devices are required. Methods based on the biological and physical properties of the cells are used to capture these cells in the blood. Early diagnosis is very important in following the prognosis of tumors of epithelial origin such as breast, lung, colon and prostate. Molecules such as EpCAM, vimentin, and cytokeratins are expressed on the surface of cells that pass into the circulation from very few primary tumors and reach secondary organs from the circulation, and are used in the diagnosis of cancer in the early stage. For example, increased EpCAM expression in breast and prostate cancer has been associated with prognosis. These molecules can be determined in some blood or body fluids to be taken from patients. However, more sensitive methods are required to be able to determine when they are at a low level according to the course of the disease. The aim is to detect these molecules found in very few cancer cells with the help of sensitive, fast-sensing biosensors, first in breast cancer cells reproduced in vitro and then in blood samples taken from breast cancer patients. In this way, cancer cells can be diagnosed early and easily and effectively treated.

Keywords: electrochemical biosensors, breast cancer, circulating tumor cells, EpCAM, Vimentin, Cytokeratins

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422 Investigation of FOXM1 Gene Expression in Breast Cancer and Its Relationship with Mir-216B-5P Expression Level

Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

Abstract:

As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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421 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

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420 Histological Grade Concordance between Core Needle Biopsy and Corresponding Surgical Specimen in Breast Carcinoma

Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

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Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

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419 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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418 Fluorescence Gold Nanoparticles: Sensing Properties and Cytotoxicity Studies in MCF-7 Human Breast Cancer Cells

Authors: Cristina Núñez, Rufina Bastida, Elena Labisbal, Alejandro Macías, María T. Pereira, José M. Vila

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A highly selective quinoline-based fluorescent sensor L was designed in order to functionalize gold nanoparticles (GNPs@L). The cytotoxicity of compound L and GNPs@L on the MCF-7 breast cancer cells was explored and it was observed that L and GNPs@L compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM).

Keywords: cytotoxicity, fluorescent probes, nanoparticles, quinoline

Procedia PDF Downloads 339
417 Facile Synthesis of Novel Substituted Aryl-Thiazole (SAT) Analogs via One-Pot Multicomponent Reaction as Potent Cytotoxic Agents against Cancer Cell Lines

Authors: Salma Mirza, Syeda Asma Naqvi, Khalid Mohammed Khan, M. Iqbal Choudhary

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In this study twenty-five (25) newly synthesized compounds substituted aryl thiazoles (SAT) 1-25 were synthesized, and in vitro cytotoxicity of these compounds was evaluated against four cancer cell lines namely, MCF-7 (ER+ve breast), MDA-MB-231 (ER-ve breast), HCT116 (colorectal), and, HeLa (cervical) and compared with the standard anticancer drug doxorubicin with IC50 value of 1.56 ± 0.05 μM. Among them, compounds 1, 4-8 and 19 were found to be active against all four cell lines. Compound 20 was found to be selectively active against MCF7 cells with IC50 value of 40.21 ± 4.15 µM, whereas compound 19 was active against only MCF7 and HeLa cells with IC50 values of 46.72 ± 1.8 and 19.86 ± 0.11 μM, respectively. These results suggest that aryl thiazoles 1 and 4 deserve to be investigated further in vivo as anti-cancer agents.

Keywords: anticancer agents, breast cancer cell lines (MCF7, MDA-MB-231), colorectal cancer cell line (HCT-116), cervical cancer cell line (HeLa), Thiazole derivatives

Procedia PDF Downloads 271
416 Dietary Patterns and Adherence to the Mediterranean Diet among Breast Cancer Female Patients in Lebanon: A Cross-Sectional Study

Authors: Yasmine Aridi, Lara Nasreddine, Maya Khalil, Arafat Tfayli, Anas Mugharbel, Farah Naja

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Breast cancer is the most commonly diagnosed cancer site among women worldwide and the second most common cause of cancer mortality. Breast cancer rates differ vastly between geographical areas, countries, and within the same country. In Lebanon, the proportion of breast cancer to all other sites of tumor is 38.2%; these rates are still lower than those observed worldwide, but remain the highest among Arab countries. Studies and evidence based reviews show a strong association between breast cancer development and prognosis and dietary habits, specifically the Mediterranean diet (MD). As such, the aim of this study is to examine dietary patterns and adherence to the MD among a sample of 182 breast cancer female patients in Beirut, Lebanon. Subjects were recruited from two major hospitals; a private medical center and a public hospital. All subjects were administered two questionnaires: socio- demographics and Mediterranean diet adherence. Five Mediterranean scores were calculated: MS, MSDPS, PMDI, PREDIMED and DDS. The mean age of the participants was 53.78 years. The overall adherence to the Mediterranean diet (MD) was low since the sample means of 3 out of the 5 calculated scores were less than the scores’ medians. Given that 4 out of the 5 Mediterranean scores significantly varied between the recruitment sites, women in the private medical center were found to adhere more to the MD. Our results also show that the majority of the sample population’s intakes are exceeding the recommendations for total and saturated fat, while meeting the requirements for fiber, EPA, DHA and Linolenic Acid. Participants in the private medical center were consuming significantly more calories, carbohydrates, fiber, sugar, Lycopene, Calcium, Iron and Folate and less fat. After conducting multivariate linear regression analyses, the following significant results were observed: positive associations between MD (CPMDI, PREDIMED) and monthly income & current state of health, while negative associations between MD (MSDPS, PREDIMED) and age & employment status. Our findings indicated a low overall adherence to the MD and identified factors associated with it; which suggests a need to address dietary habits among BC patients in Lebanon, specifically encouraging them to adhere to their traditional Mediterranean diet.

Keywords: Adherence, Breast cancer, Dietary patterns, Mediterranean diet, Nutrition

Procedia PDF Downloads 377
415 Cancer Stem Cell-Associated Serum Proteins Obtained by Maldi TOF/TOF Mass Spectrometry in Women with Triple-Negative Breast Cancer

Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

Abstract:

Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

Procedia PDF Downloads 180
414 O2 Saturation Comparison Between Breast Milk Feeding and Tube Feeding in Very Low Birth Weight Neonates

Authors: Ashraf Mohammadzadeh, Ahmad Shah Farhat, Azin Vaezi, Aradokht Vaezi

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Background & Aim: Preterm infants born at less than 34 weeks postconceptional age are not as neurologically mature as their term counterparts and thus have difficulty coordinating sucking, swallowing and breathing. As a result, they are traditionally gavage fed until they are able to oral feed successfully. The aim of study was to evaluate comparative effect of orogastric and breast feeding on oxygen saturation in very low birth weight infant (<1500gm). Patients and Methods: In this clinical trial all babies admitted in the Neonatal Research Center of Imamreza Hospital, Mashhad during a 4 months period were elected. Criteria for entrance to study included birth weight ≤ 1500 grams, exclusive breastfeeding, having no special problem after 48 hours, receivinge only routine care and intake of milk was 100cc/kg/day. Each neonate received two rounds of orogastric and breast feeding in the morning and in the afternoon, during which mean oxygen saturation was measured by pulse-oxymetry. During the study the heart rate and temperature of the neonates were monitored, and in case of hypothermia, bradycardia(less than 100 per minute) or apnea the feeding was discontinued and the study was repeated the following day. Data analysis was carried out using SPSS. Results: Fifty neonates were studied. The average birth weight was 1267.20±165.42 grams and average gestational age was 31.81±1.92 and female/male ratio was 1.2. There was no significant statistical difference in arterial oxygen saturation in orogastric and breast feeding in the morning and in the afternoon. (p=0.16 in the morning and p=0.6 in the afternoon). There was no complication of apnea, hypothermia or bradycardia. Conclusion: There was no significant statistical difference between the two methods in arterial oxygen saturation. It seems that oral feeding (which is a natural route) and skin contact between the mother and neonate causes a strong emotional bonding between the two and brings about better social adaptation for the neonate. Also shorter period of stay in hospital is more preferred, and breast feeding should be started at the earliest possible time after birth.

Keywords: Very low birth weight (V.L.B.W), O2 Saturation, Breast Feeding, Tube Feeding

Procedia PDF Downloads 56
413 Emerging Therapeutic Approach with Dandelion Phytochemicals in Breast Cancer Treatment

Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui

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Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.

Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical

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412 Optimizing Exposure Parameters in Digital Mammography: A Study in Morocco

Authors: Talbi Mohammed, Oustous Aziz, Ben Messaoud Mounir, Sebihi Rajaa, Khalis Mohammed

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Background: Breast cancer is the leading cause of death for women around the world. Screening mammography is the reference examination, due to its sensitivity for detecting small lesions and micro-calcifications. Therefore, it is essential to ensure quality mammographic examinations with the most optimal dose. These conditions depend on the choice of exposure parameters. Clinically, practices must be evaluated in order to determine the most appropriate exposure parameters. Material and Methods: We performed our measurements on a mobile mammography unit (PLANMED Sofie-classic.) in Morocco. A solid dosimeter (AGMS Radcal) and a MTM 100 phantom allow to quantify the delivered dose and the image quality. For image quality assessment, scores are defined by the rate of visible inserts (MTM 100 phantom), obtained and compared for each acquisition. Results: The results show that the parameters of the mammography unit on which we have made our measurements can be improved in order to offer a better compromise between image quality and breast dose. The last one can be reduced up from 13.27% to 22.16%, while preserving comparable image quality.

Keywords: Mammography, Breast Dose, Image Quality, Phantom

Procedia PDF Downloads 134
411 Comparison of an Anthropomorphic PRESAGE® Dosimeter and Radiochromic Film with a Commercial Radiation Treatment Planning System for Breast IMRT: A Feasibility Study

Authors: Khalid Iqbal

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This work presents a comparison of an anthropomorphic PRESAGE® dosimeter and radiochromic film measurements with a commercial treatment planning system to determine the feasibility of PRESAGE® for 3D dosimetry in breast IMRT. An anthropomorphic PRESAGE® phantom was created in the shape of a breast phantom. A five-field IMRT plan was generated with a commercially available treatment planning system and delivered to the PRESAGE® phantom. The anthropomorphic PRESAGE® was scanned with the Duke midsized optical CT scanner (DMOS-RPC) and the OD distribution was converted to dose. Comparisons were performed between the dose distribution calculated with the Pinnacle3 treatment planning system, PRESAGE®, and EBT2 film measurements. DVHs, gamma maps, and line profiles were used to evaluate the agreement. Gamma map comparisons showed that Pinnacle3 agreed with PRESAGE® as greater than 95% of comparison points for the PTV passed a ± 3%/± 3 mm criterion when the outer 8 mm of phantom data were discluded. Edge artifacts were observed in the optical CT reconstruction, from the surface to approximately 8 mm depth. These artifacts resulted in dose differences between Pinnacle3 and PRESAGE® of up to 5% between the surface and a depth of 8 mm and decreased with increasing depth in the phantom. Line profile comparisons between all three independent measurements yielded a maximum difference of 2% within the central 80% of the field width. For the breast IMRT plan studied, the Pinnacle3 calculations agreed with PRESAGE® measurements to within the ±3%/± 3 mm gamma criterion. This work demonstrates the feasibility of the PRESAGE® to be fashioned into anthropomorphic shape, and establishes the accuracy of Pinnacle3 for breast IMRT. Furthermore, these data have established the groundwork for future investigations into 3D dosimetry with more complex anthropomorphic phantoms.

Keywords: 3D dosimetry, PRESAGE®, IMRT, QA, EBT2 GAFCHROMIC film

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410 In vitro Comparison Study of Biologically Synthesized Cupper-Disulfiram Nanoparticles with Its Free Corresponding Complex as Therapeutic Approach for Breast and Liver Cancer

Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

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The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

Procedia PDF Downloads 162
409 Synthesis and Cytotoxic Activity of New Quinazolinone-Based Compounds against Human Breast Cancer Cell Line MCF-7

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

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

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

Procedia PDF Downloads 459
408 Coumestrol Induced Apoptosis in Breast Cancer MCF-7 Cells via Redox Cycling of Copper and ROS Generation: Implications of Copper Chelation Strategy in Cancer Treatment

Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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407 Concealing Breast Cancer Status: A Qualitative Study in India

Authors: Shradha Parsekar, Suma Nair, Ajay Bailey, Binu V. S.

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Background: Concealing of cancer-related information is seen in many low-and-middle-income countries and may be associated with multiple factors. Comparatively, there is lack of information about, how breast cancers diagnosed women disclose cancer-related information to their social contacts and vice versa. To get more insights on the participant’s experience, opinions, expectations, and attitudes, a qualitative study is a suitable approach. Therefore, this study involving in-depth interviews was planned to lessen this gap. Methods: Interviews were conducted separately among breast cancer patients and their caregivers with semi-structured qualitative interview guide. Purposive and convenient sampling was being used to recruit patients and caregivers, respectively. Ethical clearance and permission from the tertiary hospital were obtained and participants were selected from the Udupi district, Karnataka, India. After obtaining a list of breast cancer diagnosed cases, participants were contacted in person and their willingness to take part in the study was taken. About 39 caregivers and 35 patients belonging to different breast cancer stages were recruited. Interviews were recorded with prior permission. Data was managed by Atlas.ti 8 software. The recordings were transcribed, translated and coded in two cycles. Most of the patients belonged to stage II and III cancer. Codes were grouped together into to whom breast cancer status was concealed to and underneath reason for the same. Main findings: followings are the codes and code families which emerged from the data. 1) Concealing the breast cancer status from social contacts other than close family members (such as extended family, neighbor and friends). Participants perceived the reasons as, a) to avoid questions which people probe (which doesn’t have answers), b) to avoid people paying courtesy visit (to inquire about the health as it is Indian culture to visit the sick person) making it inconvenient for patient and caregivers have to offer something and talk to them, c) to avoid people getting shocked (react as if cancer is different from other diseases) or getting emotional/sad, or getting fear of death d) to avoid getting negative suggestion or talking anything in front of patient as it may affect patient negatively, e) to avoid getting stigmatized, f) to avoid getting obstacle in child’s marriage. 2) Participant concealed the breast cancer status of young children as they perceived that it may a) affect studies, b) affect emotionally, c) children may get scared. 3) Concealing the breast cancer status from patients as the caregivers perceived that they have fear of a) worsening patient’s health, b) patient getting tensed, c) patient getting shocked, and d) patient getting scared. However, some participants stressed important in disclosing the cancer status to social contact/patient to make the people aware of the disease. Conclusion: The news of breast cancer spreads like electricity in the wire, therefore, patient or family avoid it for many reasons. Although, globally, due to physicians’ ethical obligations, there is an inclination towards more disclosure of cancer diagnosis and status of prognosis to the patient. However, it is an ongoing argument whether patient/social contacts should know the status especially in a country like India.

Keywords: breast cancer, concealing cancer status, India, qualitative study

Procedia PDF Downloads 108
406 Dual-Channel Reliable Breast Ultrasound Image Classification Based on Explainable Attribution and Uncertainty Quantification

Authors: Haonan Hu, Shuge Lei, Dasheng Sun, Huabin Zhang, Kehong Yuan, Jian Dai, Jijun Tang

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This paper focuses on the classification task of breast ultrasound images and conducts research on the reliability measurement of classification results. A dual-channel evaluation framework was developed based on the proposed inference reliability and predictive reliability scores. For the inference reliability evaluation, human-aligned and doctor-agreed inference rationals based on the improved feature attribution algorithm SP-RISA are gracefully applied. Uncertainty quantification is used to evaluate the predictive reliability via the test time enhancement. The effectiveness of this reliability evaluation framework has been verified on the breast ultrasound clinical dataset YBUS, and its robustness is verified on the public dataset BUSI. The expected calibration errors on both datasets are significantly lower than traditional evaluation methods, which proves the effectiveness of the proposed reliability measurement.

Keywords: medical imaging, ultrasound imaging, XAI, uncertainty measurement, trustworthy AI

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405 Diagnostic Accuracy Of Core Biopsy In Patients Presenting With Axillary Lymphadenopathy And Suspected Non-Breast Malignancy

Authors: Monisha Edirisooriya, Wilma Jack, Dominique Twelves, Jennifer Royds, Fiona Scott, Nicola Mason, Arran Turnbull, J. Michael Dixon

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Introduction: Excision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy. Methods: Between 2009 and 2019, 165 patients referred to the Edinburgh Breast Unit had a total of 179 axillary lymph node core biopsies. Results: 152 (92%) of the 165 initial core biopsies were deemed to contain adequate nodal tissue. Core biopsy correctly established malignancy in 75 of the 78 patients with haematological malignancy (96%) and in all 28 patients with metastatic carcinoma (100%) and correctly diagnosed benign changes in 49 of 57 (86%) patients with benign conditions. There were no false positives and no false negatives. In 67 (85.9%) of the 78 patients with hematological malignancy, there was sufficient material in the first core biopsy to allow the pathologist to make an actionable diagnosis and not ask for more tissue sampling prior to treatment. There were no complications of core biopsy. On follow up, none of the patients with benign cores has been shown to have malignancy in the axilla and none with lymphoma had their initial disease incorrectly classified. Conclusions: This study shows that core biopsy is now the investigation of choice for patients presenting with axillary lymphadenopathy even in those suspected as having lymphoma.

Keywords: core biopsy, excision biopsy, axillary lymphadenopathy, non-breast malignancy

Procedia PDF Downloads 214