Search results for: breast displacement
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1597

Search results for: breast displacement

1357 Estimation of Stress Intensity Factors from near Crack Tip Field

Authors: Zhuang He, Andrei Kotousov

Abstract:

All current experimental methods for determination of stress intensity factors are based on the assumption that the state of stress near the crack tip is plane stress. Therefore, these methods rely on strain and displacement measurements made outside the near crack tip region affected by the three-dimensional effects or by process zone. In this paper, we develop and validate an experimental procedure for the evaluation of stress intensity factors from the measurements of the out-of-plane displacements in the surface area controlled by 3D effects. The evaluation of stress intensity factors is possible when the process zone is sufficiently small, and the displacement field generated by the 3D effects is fully encapsulated by K-dominance region.

Keywords: digital image correlation, stress intensity factors, three-dimensional effects, transverse displacement

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1356 Synergistic Effect of Doxorubicin-Loaded Silver Nanoparticles – Polymeric Conjugates on Breast Cancer Cells

Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

Abstract:

Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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1355 The Analysis of Personalized Low-Dose Computed Tomography Protocol Based on Cumulative Effective Radiation Dose and Cumulative Organ Dose for Patients with Breast Cancer with Regular Chest Computed Tomography Follow up

Authors: Okhee Woo

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Purpose: The aim of this study is to evaluate 2-year cumulative effective radiation dose and cumulative organ dose on regular follow-up computed tomography (CT) scans in patients with breast cancer and to establish personalized low-dose CT protocol. Methods and Materials: A retrospective study was performed on the patients with breast cancer who were diagnosed and managed consistently on the basis of routine breast cancer follow-up protocol between 2012-01 and 2016-06. Based on ICRP (International Commission on Radiological Protection) 103, the cumulative effective radiation doses of each patient for 2-year follow-up were analyzed using the commercial radiation management software (Radimetrics, Bayer healthcare). The personalized effective doses on each organ were analyzed in detail by the software-providing Monte Carlo simulation. Results: A total of 3822 CT scans on 490 patients was evaluated (age: 52.32±10.69). The mean scan number for each patient was 7.8±4.54. Each patient was exposed 95.54±63.24 mSv of radiation for 2 years. The cumulative CT radiation dose was significantly higher in patients with lymph node metastasis (p = 0.00). The HER-2 positive patients were more exposed to radiation compared to estrogen or progesterone receptor positive patient (p = 0.00). There was no difference in the cumulative effective radiation dose with different age groups. Conclusion: To acknowledge how much radiation exposed to a patient is a starting point of management of radiation exposure for patients with long-term CT follow-up. The precise and personalized protocol, as well as iterative reconstruction, may reduce hazard from unnecessary radiation exposure.

Keywords: computed tomography, breast cancer, effective radiation dose, cumulative organ dose

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1354 Using Econometric Methods to Explore Obesity Stigma and Avoidance of Breast and Cervical Cancer Screening

Authors: Stephanie A. Schauder, Gosia Sylwestrzak

Abstract:

Overweight and obese women report avoiding preventive care due to fear of weight-related bias from medical professionals. Gynecological exams, due to their sensitive and personally invasive nature, are especially susceptible to avoidance. This research investigates the association between body mass index (BMI) and screening rates for breast and cervical cancer using claims data from 1.3 million members of a large health insurance company. Because obesity is associated with increased cancer risk, screenings for these cancers should increase as BMI increases. However, this paper finds that the distribution of cancer screening rates by BMI take an inverted U-shape with underweight and obese members having the lowest screening rates. For cervical cancer screening, those in the target population with a BMI of 23 have the highest screening rate at 68%, while Obese Class III members have a screening rate of 50%. Those in the underweight category have a screening rate of 58%. This relationship persists even after controlling for health and demographic covariates in regression analysis. Interestingly, there is no association between BMI and BRCA (BReast CAncer gene) genetic testing. This is consistent with the narrative that stigma causes avoidance because genetic testing does not involve any assessment of a person’s body. More work must be done to determine how to increase cancer screening rates in those who may feel stigmatized due to their weight.

Keywords: cancer screening, cervical cancer, breast cancer, weight stigma, avoidance of care

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1353 The Effect of Different Parameters on a Single Invariant Lateral Displacement Distribution to Consider the Higher Modes Effect in a Displacement-Based Pushover Procedure

Authors: Mohamad Amin Amini, Mehdi Poursha

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Nonlinear response history analysis (NL-RHA) is a robust analytical tool for estimating the seismic demands of structures responding in the inelastic range. However, because of its conceptual and numerical complications, the nonlinear static procedure (NSP) is being increasingly used as a suitable tool for seismic performance evaluation of structures. The conventional pushover analysis methods presented in various codes (FEMA 356; Eurocode-8; ATC-40), are limited to the first-mode-dominated structures, and cannot take higher modes effect into consideration. Therefore, since more than a decade ago, researchers developed enhanced pushover analysis procedures to take higher modes effect into account. The main objective of this study is to propose an enhanced invariant lateral displacement distribution to take higher modes effect into consideration in performing a displacement-based pushover analysis, whereby a set of laterally applied displacements, rather than forces, is monotonically applied to the structure. For this purpose, the effect of different parameters such as the spectral displacement of ground motion, the modal participation factor, and the effective modal participating mass ratio on the lateral displacement distribution is investigated to find the best distribution. The major simplification of this procedure is that the effect of higher modes is concentrated into a single invariant lateral load distribution. Therefore, only one pushover analysis is sufficient without any need to utilize a modal combination rule for combining the responses. The invariant lateral displacement distribution for pushover analysis is then calculated by combining the modal story displacements using the modal combination rules. The seismic demands resulting from the different procedures are compared to those from the more accurate nonlinear response history analysis (NL-RHA) as a benchmark solution. Two structures of different heights including 10 and 20-story special steel moment resisting frames (MRFs) were selected and evaluated. Twenty ground motion records were used to conduct the NL-RHA. The results show that more accurate responses can be obtained in comparison with the conventional lateral loads when the enhanced modal lateral displacement distributions are used.

Keywords: displacement-based pushover, enhanced lateral load distribution, higher modes effect, nonlinear response history analysis (NL-RHA)

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1352 Chatter Suppression in Boring Process Using Passive Damper

Authors: V. Prasannavenkadesan, A. Elango, S. Chockalingam

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During machining process, chatter is an unavoidable phenomenon. Boring bars possess the cantilever shape and due to this, it is subjected to chatter. The adverse effect of chatter includes the increase in temperature which will leads to excess tool wear. To overcome these problems, in this investigation, Cartridge brass (Cu – 70% and Zn – 30%) is passively fixed on the boring bar and also clearance is provided in order to reduce the displacement, tool wear and cutting temperature. A conventional all geared lathe is attached with vibrometer and pyrometer is used to measure the displacement and temperature. The influence of input parameters such as cutting speed, depth of cut and clearance on temperature, tool wear and displacement are investigated for various cutting conditions. From the result, the optimum conditions to obtain better damping in boring process for chatter reduction is identified.

Keywords: boring, chatter, mass damping, passive damping

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1351 The Subaltern Woman and the Reproductive Body - A Reading of Devi's 'Breast Stories'

Authors: Sharon Lopez

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Much of critical thought dismisses the notion of subaltern women engaging in resistance because of her complex colonial identity. She is seen in postcolonial theory as being "doubly effaced" and removed from exercising control to speak up and taking part in defiance. This line of reasoning suggests a critical area in which engaging with issues unavoidably excludes subaltern women from the emerging resistance discourse. A position like this also suggests a closed-minded view of human experience and a desire to maintain subalternity. The argument here is that subaltern women might be understood as achieving agency when they engage in resistance and speak out about their circumstances, whether aloud or in silence. Using deductions from Mahasweta Devi's literary narratives such as Imaginary Maps and Breast Stories, the study investigates the tactics Devi employs to engage marginalised women into resistance and establishes that the 'body' emerges in her stories not just as a site of oppression but also as an important motif of power and resistance.

Keywords: subaltern woman, reproductive docy, breast giver, devi

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1350 Triggering Apoptosis to Uproot Breast Cancer: HPLC-MS/MS Profiling, in-vitro and in-silico Fascinating Results of Polyphenolics in Pomegranate Rind Extract

Authors: Alaa M. Badr Eldin, Mayar M. Shahen, Mohammed S. Sedeek, Marwa I. Ezzat, Sawsan M. ElSonbaty, Muhammed A. Saad, Manal S. Afifi, Omar M. Sabry

Abstract:

Using HPLC-MS/MS technique, 133 polyphenolic compounds were identified in the methanol extract of pomegranate rind (Punica granatum L.). In-vitro cytotoxic activity against breast cancer cell line MCF-7 was investigated, with an IC50 of 54 ug/ml. In-silico molecular docking using ellagic acid, gallagic acid, and Punicalagin as model compounds identified in pomegranate rind extract confirmed the intriguing anti-estrogenic action of the key polyphenolic components in pomegranate rind extract. Surprisingly, taxol showed low activity compared to pomegranate compounds as ERα antagonist and ERβ agonist. Pomegranate rind extract enhanced apoptosis of breast cancer cells through upregulation of the caspase-3 expression and downregulation of NF-κB transcription factor.

Keywords: HPLC-MS/MS, pomegranate rind, cytotoxicity, MCF-7, ER, caspase-3, NF-kB

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1349 Breast Cancer Incidence Estimation in Castilla-La Mancha (CLM) from Mortality and Survival Data

Authors: C. Romero, R. Ortega, P. Sánchez-Camacho, P. Aguilar, V. Segur, J. Ruiz, G. Gutiérrez

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Introduction: Breast cancer is a leading cause of death in CLM. (2.8% of all deaths in women and 13,8% of deaths from tumors in womens). It is the most tumor incidence in CLM region with 26.1% from all tumours, except nonmelanoma skin (Cancer Incidence in Five Continents, Volume X, IARC). Cancer registries are a good information source to estimate cancer incidence, however the data are usually available with a lag which makes difficult their use for health managers. By contrast, mortality and survival statistics have less delay. In order to serve for resource planning and responding to this problem, a method is presented to estimate the incidence of mortality and survival data. Objectives: To estimate the incidence of breast cancer by age group in CLM in the period 1991-2013. Comparing the data obtained from the model with current incidence data. Sources: Annual number of women by single ages (National Statistics Institute). Annual number of deaths by all causes and breast cancer. (Mortality Registry CLM). The Breast cancer relative survival probability. (EUROCARE, Spanish registries data). Methods: A Weibull Parametric survival model from EUROCARE data is obtained. From the model of survival, the population and population data, Mortality and Incidence Analysis MODel (MIAMOD) regression model is obtained to estimate the incidence of cancer by age (1991-2013). Results: The resulting model is: Ix,t = Logit [const + age1*x + age2*x2 + coh1*(t – x) + coh2*(t-x)2] Where: Ix,t is the incidence at age x in the period (year) t; the value of the parameter estimates is: const (constant term in the model) = -7.03; age1 = 3.31; age2 = -1.10; coh1 = 0.61 and coh2 = -0.12. It is estimated that in 1991 were diagnosed in CLM 662 cases of breast cancer (81.51 per 100,000 women). An estimated 1,152 cases (112.41 per 100,000 women) were diagnosed in 2013, representing an increase of 40.7% in gross incidence rate (1.9% per year). The annual average increases in incidence by age were: 2.07% in women aged 25-44 years, 1.01% (45-54 years), 1.11% (55-64 years) and 1.24% (65-74 years). Cancer registries in Spain that send data to IARC declared 2003-2007 the average annual incidence rate of 98.6 cases per 100,000 women. Our model can obtain an incidence of 100.7 cases per 100,000 women. Conclusions: A sharp and steady increase in the incidence of breast cancer in the period 1991-2013 is observed. The increase was seen in all age groups considered, although it seems more pronounced in young women (25-44 years). With this method you can get a good estimation of the incidence.

Keywords: breast cancer, incidence, cancer registries, castilla-la mancha

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1348 Efficiency of the Strain Based Approach Formulation for Plate Bending Analysis

Authors: Djamal Hamadi, Sifeddine Abderrahmani, Toufik Maalem, Oussama Temami

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In recent years many finite elements have been developed for plate bending analysis. The formulated elements are based on the strain based approach. This approach leads to the representation of the displacements by higher order polynomial terms without the need for the introduction of additional internal and unnecessary degrees of freedom. Good convergence can also be obtained when the results are compared with those obtained from the corresponding displacement based elements, having the same total number of degrees of freedom. Furthermore, the plate bending elements are free from any shear locking since they converge to the Kirchhoff solution for thin plates contrarily for the corresponding displacement based elements. In this paper the efficiency of the strain based approach compared to well known displacement formulation is presented. The results obtained by a new formulated plate bending element based on the strain approach and Kirchhoff theory are compared with some others elements. The good convergence of the new formulated element is confirmed.

Keywords: displacement fields, finite elements, plate bending, Kirchhoff theory, strain based approach

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1347 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

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1346 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

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1345 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

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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

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1344 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

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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

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1343 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

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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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1342 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

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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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1341 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

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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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1340 Interaction between Trapezoidal Hill and Subsurface Cavity under SH Wave Incidence

Authors: Yuanrui Xu, Zailin Yang, Yunqiu Song, Guanxixi Jiang

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It is an important subject of seismology on the influence of local topography on ground motion during earthquake. In mountainous areas with complex terrain, the construction of the tunnel is often the most effective transportation scheme. In these projects, the local terrain can be simplified into hills with different shapes, and the underground tunnel structure can be regarded as a subsurface cavity. The presence of the subsurface cavity affects the strength of the rock mass and changes the deformation and failure characteristics. Moreover, the scattering of the elastic waves by underground structures usually interacts with local terrains, which leads to a significant influence on the surface displacement of the terrains. Therefore, it is of great practical significance to study the surface displacement of local terrains with underground tunnels in earthquake engineering and seismology. In this work, the region is divided into three regions by the method of region matching. By using the fractional Bessel function and Hankel function, the complex function method, and the wave function expansion method, the wavefield expression of SH waves is introduced. With the help of a constitutive relation between the displacement and the stress components, the hoop stress and radial stress is obtained subsequently. Then, utilizing the continuous condition at different region boundaries, the undetermined coefficients in wave fields are solved by the Fourier series expansion and truncation of the finite term. Finally, the validity of the method is verified, and the surface displacement amplitude is calculated. The surface displacement amplitude curve is discussed in the numerical results. The results show that different parameters, such as radius and buried depth of the tunnel, wave number, and incident angle of the SH wave, have a significant influence on the amplitude of surface displacement. For the underground tunnel, the increase of buried depth will make the response of surface displacement amplitude increases at first and then decreases. However, the increase of radius leads the response of surface displacement amplitude to appear an opposite phenomenon. The increase of SH wave number can enlarge the amplitude of surface displacement, and the change of incident angle can obviously affect the amplitude fluctuation.

Keywords: method of region matching, scattering of SH wave, subsurface cavity, trapezoidal hill

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1339 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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1338 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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1337 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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1336 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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1335 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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1334 Determination of Circulating Tumor Cells in Breast Cancer Patients by Electrochemical Biosensor

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

Abstract:

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

Procedia PDF Downloads 226
1333 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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1332 Automatic Early Breast Cancer Segmentation Enhancement by Image Analysis and Hough Transform

Authors: David Jurado, Carlos Ávila

Abstract:

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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1331 Soil-Structure Interaction in a Case Study Bridge: Seismic Response under Moderate and Strong Near-Fault Earthquakes

Authors: Nastaran Cheshmehkaboodi, Lotfi Guizani, Noureddine Ghlamallah

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Seismic isolation proves to be a powerful technology in reducing seismic hazards and enhancing overall structural resilience. However, the performance of the technology can be influenced by various factors, including seismic inputs and soil conditions. This research aims to investigate the effects of moderate and strong earthquakes associated with different distances of the source on the seismic responses of conventional and isolated bridges, considering the soil-structure interaction effects. Two groups of moderate and strong near-fault records are applied to the conventional and isolated bridges, with and without considering the underlying soil. For this purpose, using the direct method, three soil properties representing rock, dense, and stiff soils are modeled in Abaqus software. Nonlinear time history analysis is carried out, and structural responses in terms of maximum deck acceleration, deck displacement, and isolation system displacement are studied. The comparison of dynamic responses between both earthquake groups demonstrates a consistent pattern, indicating that the bridge performance and the effects of soil-structure interaction are primarily influenced by the ground motions and their frequency contents. Low ratios of PGA/PGV are found to significantly impact all dynamic responses, resulting in higher force and displacement responses, regardless of the distance associated with the ruptured fault. In addition, displacement responses increase drastically on softer soils. Thus, meticulous consideration is crucial in designing isolation systems to avoid underestimating displacement demands and to ensure sufficient displacement capacity. Despite a lower PGA value in high seismicity areas in this study, the acceleration demand during strong earthquakes is up to 1.3 times higher in conventional bridges and up to 3 times higher in isolated bridges than in moderate earthquakes. Additionally, the displacement demand in strong earthquakes is up to 2 times higher in conventional bridges and up to 5 times higher in isolated bridges compared to moderate earthquakes, highlighting the increased force and displacement demand in strong earthquakes.

Keywords: bridges, seismic isolation, near-fault, earthquake characteristics, soil-structure interaction

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1330 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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1329 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

Procedia PDF Downloads 517
1328 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

Abstract:

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 342