Search results for: breast cancer cell lines
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6129

Search results for: breast cancer cell lines

5529 Automatic Identification of Pectoral Muscle

Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

Abstract:

Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

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5528 Correlation Between Different Radiological Findings and Histopathological diagnosis of Breast Diseases: Retrospective Review Conducted Over Sixth Years in King Fahad University Hospital in Eastern Province, Saudi Arabia

Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

Abstract:

The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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5527 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

Abstract:

Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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5526 Chemical Composition of Essential Oil and in vitro Antibacterial and Anticancer Activity of the Hydroalcolic Extract from Coronilla varia

Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

Abstract:

The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

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5525 The Regulation of the Cancer Epigenetic Landscape Lies in the Realm of the Long Non-coding RNAs

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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5524 Deformation of Metallic Foams with Closed Cell at High Temperatures

Authors: Emrah Ersoy, Yusuf Ozcatalbas

Abstract:

The aim of this study is to investigate formability of Al based closed cell metallic foams at high temperature. The foam specimens with rectangular section were produced from AlMg1Si0.6TiH20.8 alloy preform material. Bending and free bending tests based on gravity effect were applied to foam specimens at high temperatures. During the tests, the time-angular deformation relationships with various temperatures were determined. Deformation types formed in cell walls were investigated by means of Scanning Electron Microscopy (SEM) and optical microscopy. Bending deformation about 90° was achieved without any defect at high temperatures. The importance of a critical temperature and deformation rate was emphasized in maintaining the deformation. Significant slip lines on surface of cell walls at tensile zones of bending specimen were observed. At high strain rates, the microcrack formation in boundaries of elongated grains was determined.

Keywords: Al alloy, Closed cell, Hot deformation, Metallic foam

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5523 The Role Support Groups Play in Decreasing Depression and PTSD in Cancer Survivors: A Literature Review

Authors: Julianne Macmullen

Abstract:

Due to advances in technology and early detection and treatment of cancer, many cancer patients are surviving longer than five years post-diagnosis. Most cancer patients suffer from depression, anxiety, and post-traumatic stress disorder (PTSD) at some point during diagnosis, treatment, and survivorship. A subgroup of patients will continue to suffer from depression and PTSD and require early intervention. Support groups provide patients with the emotional and informational support they require while also giving survivors a sense of community, friendship, and purpose. This type of support is recognized by researchers to improve the quality of life while also decreasing depression and PTSD symptoms. The gaps in the literature include cultural diversity, minorities, and support groups involving cancer types other than breast cancer. Another gap in the literature includes the perceptions of cancer patients as well as longitudinal studies to determine the relationships between support groups and decreased depression and PTSD rates over time. Future research is required to fill the gaps in the literature mentioned previously. Future research is also needed to analyze the difference in age groups and different types of support groups such as professionally-led, peer-led, and online. Implications for practice involve providers assessing for the symptoms of depression and PTSD in order to offer prompt treatment and support services to those patients. In conclusion, social support by way of support groups improves the quality of life, gives survivors a sense of purpose to help others while also gaining the support they need, and reduces the rate of depressive episodes related to PTSD.

Keywords: cancer survivor, survivorship, post-traumatic stress disorder (PTSD), depression, support groups

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5522 Comparison of 18F-FDG and 11C-Methionine PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

Abstract:

Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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5521 Identification of Clinical Characteristics from Persistent Homology Applied to Tumor Imaging

Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

Abstract:

The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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5520 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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5519 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer

Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

Abstract:

Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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5518 Production of Single-Chain Antibodies against Common Epitopes of ErbB1 and ErbB2 Using Phage Display Antibody Library

Authors: Gholamreza Hashemitabr, Reza Valadan, Alireza Rafiei, Mohammad Reza Bassami

Abstract:

Breast cancer is the most common malignancy among women worldwide. Cancer cells use a complex multilayer network of epidermal growth factor receptors (EGFRs) signaling pathways to support their survival and growth. The overlapping networks of EGFRs signaling pathways account for the failure of most ErbB-targeted therapies. The aim of this study was to enrich a pool of recombinant antibody fragments against common epitopes of ErbB1 and ErbB2 in order to simultaneous blockade of ErbBs signaling pathways. ErbB1 and ErbB2 were expressed stably in VERO cells. Selection of recombinant antibodies was performed on live cells expressing either of ErbB1 and ErbB2 receptors using subtractive phage display approach. The results of PCR and DNA fingerprinting in the last round of panning showed that most clones contained insert (80% and 85% for ErbB1 and ErbB2 respectively) with an identical restriction pattern. The selected clones showed positive reaction to both ErbB1 and ErbB2 receptors in phage-ELISA test. Furthermore, the resulting soluble antibody fragments recognized common epitopes of both immunoprecipitated ErbB1 and ErbB2 in western blot. Additionally, the antibodies directed against the dimerization domain of ErbB1 demonstrated a significant absorbance in EGF-stimulated VERO/ErbB1 cells than non-stimulated cells (1.91 and 1.09 respectively). Moreover, the results of dimerization inhibition test showed that these antibodies blocked ErbB1 and ErbB2 dimerization on the surface of ErbB1 and ErbB2 expressing VERO cells. Regarding the importance of pan-ErbB approach to cancer therapy, the antibodies developed here might provide novel therapeutics for simultaneous blockade of ErbBs signaling pathways.

Keywords: breast cancer, single-chain antibody, ErbB1, ErbB2, epitope

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5517 Azadirachta indica Derived Protein Encapsulated Novel Guar Gum Nanocapsules against Colon Cancer

Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

Abstract:

Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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5516 Antioxidant and Anticancer Activities of Ethanolic Extract from Monascus purpureus

Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

Abstract:

Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.

Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract

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5515 Content-Based Mammograms Retrieval Based on Breast Density Criteria Using Bidimensional Empirical Mode Decomposition

Authors: Sourour Khouaja, Hejer Jlassi, Nadia Feddaoui, Kamel Hamrouni

Abstract:

Most medical images, and especially mammographies, are now stored in large databases. Retrieving a desired image is considered of great importance in order to find previous similar cases diagnosis. Our method is implemented to assist radiologists in retrieving mammographic images containing breast with similar density aspect as seen on the mammogram. This is becoming a challenge seeing the importance of density criteria in cancer provision and its effect on segmentation issues. We used the BEMD (Bidimensional Empirical Mode Decomposition) to characterize the content of images and Euclidean distance measure similarity between images. Through the experiments on the MIAS mammography image database, we confirm that the results are promising. The performance was evaluated using precision and recall curves comparing query and retrieved images. Computing recall-precision proved the effectiveness of applying the CBIR in the large mammographic image databases. We found a precision of 91.2% for mammography with a recall of 86.8%.

Keywords: BEMD, breast density, contend-based, image retrieval, mammography

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5514 Adherence to Dietary Approaches to Stop Hypertension-Style Diet and Risk of Mortality from Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Authors: Roohallah Fallah-Moshkani, Mohammad Ali Mohsenpour, Reza Ghiasvand, Hossein Khosravi-Boroujeni, Seyed Mehdi Ahmadi, Paula Brauer, Amin Salehi-Abargouei

Abstract:

Purpose: Several investigations have proposed the protective association between dietary approaches to stop hypertension (DASH) style diet and risk of cancers; however, they have led to inconsistent results. The present study aimed to systematically review the prospective cohort studies conducted in this regard and, if possible, to quantify the overall effect of using meta-analysis. Methods: PubMed, EMBASE, Scopus, and Google Scholar were searched for cohort studies published up to December 2017. Relative risks (RRs) which were reported for fully adjusted models and their confidence intervals were extracted for meta-analysis. Random effects model was incorporated to combine the RRs. Results: Sixteen studies were eligible to be included in the systematic review from which 8 reports were conducted on the effect of DASH on the risk of mortality from all cancer types, four on the risk of colorectal cancer, and three on the risk of colon and rectal cancer. Four studies examined the association with other cancers (breast, hepatic, endometrial, and lung cancer). Meta-analysis showed that high concordance with DASH significantly decreases the risk of all cancer types (RR=0.83, 95% confidence interval (95%CI):0.80-0.85); furthermore participants who highly adhered to the DASH had lower risk of developing colorectal (RR=0.79, 95%CI: 0.75-0.83), colon (RR=0.81, 95%CI: 0.74-0.87) and rectal (RR=0.79, 95%CI: 0.63-0.98) cancer compared to those with the lowest adherence. Conclusions: DASH-style diet should be suggested as a healthy approach to protect from cancer in the community. Prospective studies exploring the effect on other cancer types and from regions other than the United States are highly recommended.

Keywords: cancer, DASH-style diet, dietary patterns, meta-analysis, systematic review

Procedia PDF Downloads 189
5513 Functionalized Single Walled Carbon Nanotubes: Targeting, Cellular Uptake, and Applications in Photodynamic Therapy

Authors: Prabhavathi Sundaram, Heidi Abrahamse

Abstract:

In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

Procedia PDF Downloads 117
5512 Synthesis and Magnetic Properties of Six-Lines Ferrihydrite Nanoparticles

Authors: Chandni Rani, S. D. Tiwari

Abstract:

Ferrihydrite is one of the distinct minerals in the family of oxides, hydroxides and oxyhydroxides of iron. It is a nanocrystalline material. It occurs naturally in different sediments, soil systems and also found in the core of ferritin, an iron storage protien. This material can also be synthesized by suitable chemical methods in laboratories. This is known as less crystalline Iron (III) Oxyhydroxide. Due to its poor crystallinity, there are very broad peaks in x-ray diffraction. Depending on the number of peaks in x-ray diffraction pattern, it is classified as two lines and six lines ferrihydrite. The average crystallite size for these two forms is found to be about 2nm to 5nm. The exact crystal structure of this system is still under debate. Out of these two forms, the six lines ferrihydrite is more ordered in comparison to two lines ferrihydrite. The magnetic behavior of two lines ferrihydrite nanoparticles is somewhat well studied. But the magnetic behavior of six lines ferrihydrite nanoparticles could not attract the attention of researchers much. This motivated us to work on the magnetic properties of six lines ferrihydrite nanoparticles. In this work, we present synthesis, structural characterization and magnetic behavior of 5 nm six lines ferrihydrite nanoparticles. X-ray diffraction and transmission electron microscope are used for structural characterization of this system. Magnetization measurements are performed to fit the data at different temperatures. Then the effect of magnetic moment distribution is also found. All these observations are discussed in detail.

Keywords: nanoparticles, magnetism, superparamagnetism, magnetic anisotropy

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5511 Mentha crispa Essential Oil and Rotundifolone Analogues: Cytotoxic Effect on Glioblastoma

Authors: Damião Sousa, Hasan Turkez, Ozlem Tozlu, Tamires Lima

Abstract:

Glioblastoma (GBM) is an aggressive cancer from the brain and with high prevalence and significant morbimortality. Therefore, it is necessary to investigate new therapeutic options against this pathology. Thus, the purpose of this study was to evaluate the antitumor activity from Mentha crispa essential oil (MCEO), its major constituent rotundifolone (ROT) and a series of six analogues on human U87MG glioblastoma cell line. The antitumor effects of the compounds on human U87MG-GBM cell line were assessed using in vitro cell viability assays. In addition, biosafety tests were performed on cultured human blood cells. The data show that MCEO, 1,2-perillaldehyde epoxide (EPER1) and perillaldehyde (PALD) were the most cytotoxic compounds against the U87MG cells, with IC50 values of 16.263, 15.087 and 14.888 μg/mL, respectively. The treatment with MCEO, EPER1 and PALD did not lead to damage in blood cells. These chemical analogues may be useful as prototypes for development of novel antitumor drugs due to their promising activities and toxicological safety.

Keywords: antitumor activity, cancer, natural products, terpenes

Procedia PDF Downloads 149
5510 Influence of Iron Content in Carbon Nanotubes on the Intensity of Hyperthermia in the Cancer Treatment

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

Abstract:

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

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

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5509 Assessment of the Radiation Absorbed Dose Produced by Lu-177, Ra-223, AC-225 for Metastatic Prostate Cancer in a Bone Model

Authors: Maryam Tajadod

Abstract:

The treatment of cancer is one of the main challenges of nuclear medicine; while cancer begins in an organ, such as the breast or prostate, it spreads to the bone, resulting in metastatic bone. In the treatment of cancer with radiotherapy, the determination of the involved tissues’ dose is one of the important steps in the treatment protocol. Comparing absorbed doses for Lu-177 and Ra-223 and Ac-225 in the bone marrow and soft tissue of bone phantom with evaluating energetic emitted particles of these radionuclides is the important aim of this research. By the use of MCNPX computer code, a model for bone phantom was designed and the values of absorbed dose for Ra-223 and Ac-225, which are Alpha emitters & Lu-177, which is a beta emitter, were calculated. As a result of research, in comparing gamma radiation for three radionuclides, Lu-177 released the highest dose in the bone marrow and Ra-223 achieved the lowest level. On the other hand, the result showed that although the figures of absorbed dose for Ra and Ac in the bone marrow are near to each other, Ra spread more energy in cortical bone. Moreover, The alpha component of the Ra-223 and Ac-225 have very little effect on bone marrow and soft tissue than a beta component of the lu-177 and it leaves the highest absorbed dose in the bone where the source is located.

Keywords: bone metastases, lutetium-177, radium-223, actinium-225, absorbed dose

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5508 Synergistic Anti-Proliferation Effect of PLK-1 Inhibitor and Livistona Chinensis Fruit Extracts on Lung Adenocarcinoma A549 Cells

Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

Abstract:

Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

Procedia PDF Downloads 142
5507 Physiological Normoxia and Cellular Adhesion of Diffuse Large B-Cell Lymphoma Primary Cells: Real-Time PCR and Immunohistochemistry Study

Authors: Kamila Duś-Szachniewicz, Kinga M. Walaszek, Paweł Skiba, Paweł Kołodziej, Piotr Ziółkowski

Abstract:

Cell adhesion is of fundamental importance in the cell communication, signaling, and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has greatly increased, and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. Unfortunately, most of the data regarding CAMs expression relates to study on cells maintained in standard oxygen condition of 21%, while the emerging evidence suggests that culturing cells in ambient air is far from physiological. In fact, oxygen in human tissues ranges from 1 to 11%. The aim of this study was to compare the effects of physiological lymph node normoxia (5% O2), and hyperoxia (21% O2) on the expression of cellular adhesion molecules of primary diffuse large B-cell lymphoma cells (DLBCL) isolated from 10 lymphoma patients. Quantitative RT-PCR and immunohistochemistry were used to confirm the differential expression of several CAMs, including ICAM, CD83, CD81, CD44, depending on the level of oxygen. Our findings also suggest that DLBCL cells maintained at ambient O2 (21%) exhibit reduced growth rate and migration ability compared to the cells growing in normoxia conditions. Taking into account all the observations, we emphasize the need to identify the optimal human cell culture conditions mimicking the physiological aspects of tumor growth and differentiation.

Keywords: adhesion molecules, diffuse large B-cell lymphoma, physiological normoxia, quantitative RT-PCR

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5506 Giant Cancer Cell Formation: A Link between Cell Survival and Morphological Changes in Cancer Cells

Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

Abstract:

Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

Procedia PDF Downloads 217
5505 Analysis and Improvement of Efficiency for Food Processing Assembly Lines

Authors: Mehmet Savsar

Abstract:

Several factors affect productivity of Food Processing Assembly Lines (FPAL). Engineers and line managers usually do not recognize some of these factors and underutilize their production/assembly lines. In this paper, a special food processing assembly line is studied in detail, and procedures are presented to illustrate how productivity and efficiency of such lines can be increased. The assembly line considered produces ten different types of freshly prepared salads on the same line, which is called mixed model assembly line. Problems causing delays and inefficiencies on the line are identified. Line balancing and related tools are used to increase line efficiency and minimize balance delays. The procedure and the approach utilized in this paper can be useful for the operation managers and industrial engineers dealing with similar assembly lines in food processing industry.

Keywords: assembly lines, line balancing, production efficiency, bottleneck

Procedia PDF Downloads 389
5504 The Anti-Allergic Activity of Prasaprohyai Preparation Extract after Accelerated Stability Testing

Authors: Sunita Makchuchit, Arunporn Itharat

Abstract:

Prasaprohyai, a Thai traditional medicine preparation listed in the Thai National List of Essential Medicines, is commonly used for treatment of fever and colds. Prasaprohyai preparation consists of 21 different plants, with Kaempferia galanga (50% w/w) as the main ingredient. The objective of this study was to investigate the anti-allergic activity of the crude extract from Prasaprohyai after accelerated stability test procedure. The method of extract used maceration in 95% ethanol and the crude extract was kept under accelerated condition at 40 ± 2 oC and 75 ± 5% relative humidity (RH) for six months. After six months of storage at 40 oC, the crude sample in various storage times (0, 15, 30, 45, 60, 90, 120, 150 and 180 days) were investigated for anti-allergic activity using IgE-sensitized RBL-2H3 cell lines. The results showed that the stability of crude ethanolic extract from Prasaprohyai under accelerated testing had no significant effect of anti-allergic activity when compared with day 0. The results showed that the ethanolic extract could be stored for two years at room temperature without loss of activity.

Keywords: accelerated stability, anti-allergy, prasaprohyai, RBL-2H3 cell lines

Procedia PDF Downloads 489
5503 An Overview of Paclitaxel as an Anti-Cancer Agent in Avoiding Malignant Metastatic Cancer Therapy

Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

Abstract:

Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

Procedia PDF Downloads 132
5502 Tumor-Biological Characteristics of Invasive Lobular Carcinoma

Authors: Sabine Danzinger, Nora Hielscher, Miriam Izso, Johanna Metzler, Carmen Trinkl, Christian Pfeifer, Kristina Tendl-Schulz, Christian F. Singer

Abstract:

The objective of this study is to analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. Methods: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). Results: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (þ), have a lower proliferation rate (Ki67 <14%), and a higher patholog- ical T stage (pT2–4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ERþ, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1–3) was significantly more frequent with ILC versus IDC. Conclusions: Our data suggests that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

Keywords: breast cancer, lobular histology, tumor biology, hormone receptor, ki67

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5501 A Review of Deep Learning Methods in Computer-Aided Detection and Diagnosis Systems based on Whole Mammogram and Ultrasound Scan Classification

Authors: Ian Omung'a

Abstract:

Breast cancer remains to be one of the deadliest cancers for women worldwide, with the risk of developing tumors being as high as 50 percent in Sub-Saharan African countries like Kenya. With as many as 42 percent of these cases set to be diagnosed late when cancer has metastasized and or the prognosis has become terminal, Full Field Digital [FFD] Mammography remains an effective screening technique that leads to early detection where in most cases, successful interventions can be made to control or eliminate the tumors altogether. FFD Mammograms have been proven to multiply more effective when used together with Computer-Aided Detection and Diagnosis [CADe] systems, relying on algorithmic implementations of Deep Learning techniques in Computer Vision to carry out deep pattern recognition that is comparable to the level of a human radiologist and decipher whether specific areas of interest in the mammogram scan image portray abnormalities if any and whether these abnormalities are indicative of a benign or malignant tumor. Within this paper, we review emergent Deep Learning techniques that will prove relevant to the development of State-of-The-Art FFD Mammogram CADe systems. These techniques will span self-supervised learning for context-encoded occlusion, self-supervised learning for pre-processing and labeling automation, as well as the creation of a standardized large-scale mammography dataset as a benchmark for CADe systems' evaluation. Finally, comparisons are drawn between existing practices that pre-date these techniques and how the development of CADe systems that incorporate them will be different.

Keywords: breast cancer diagnosis, computer aided detection and diagnosis, deep learning, whole mammogram classfication, ultrasound classification, computer vision

Procedia PDF Downloads 93
5500 Ellagic Acid Enhanced Apoptotic Radiosensitivity via G1 Cell Cycle Arrest and γ-H2AX Foci Formation in HeLa Cells in vitro

Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

Abstract:

Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

Procedia PDF Downloads 356