Search results for: cancer research

Authors: Ghasem Yazadani, Hamidreza Ahmadi, Masoud Ahmadi, Sajad Rezazadeh

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In this paper with designing and proposing a compound of a heating and cooling system has been tried to show effect of this system on preventing esophagus cancer that can be caused by hot and cold drinks such as tea, coffee and ice water. This system has been simulated mechanically by fluent software and also has been validated by experimental way and a comprehensive result has been presented. Both of solution ways show that this system can reduce or increase temperature of drink to safe very dramatically and it can be a huge step toward consuming drinks safely and also it can be efficient about time issues. The system consists of a temperature sensor and an electronic controller that has a computer program to act automatically this task. Also this system has been presented after many different simulations and has been tried to find the best one in the point view of velocity of heating and cooling.

Keywords: fluent, heat transfer, controller, esophagus cancer

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Authors: Abujnah Dukali

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Natural honey was assessed in cell culture system for its anticancer activity. Human leukemic cell line HL 60 was treated with honey and cultured for 5 days and cytotoxicity was calculated by MTT assay. Honey showed cytotoxicity with CC50 value of 174.20 µg/ml. Radical modulation activities was assessed by lipid peroxidation assay using egg lecithin. Honey showed antioxidant activity with EC50 value of 159.73 µg/ml. In addition, treatment with HL60 cells also resulted in nuclear DNA fragmentation, as seen in agarose gel electrophoresis. This is a hallmark of cells undergoing apoptosis. Confirmation of apoptosis was performed by staining the cells with Annexin V and FACS analysis. Apoptosis is an active, genetically regulated disassembly of the cell form within. Disassembly creates changes in the phospholipid content of the cytoplasmic membrane outer leaflet. Phosphatidylserine (PS) is translocated from the inner to the outer surface of the cell for phagocytic cell recognition. The human anticoagulant, annexin V, is a Ca2+-dependent phospholipid protein with a high affinity for PS. Annexin V labeled with fluorescein can identify apoptotic cells in the population It is a confirmatory test for apoptosis. Annexin V-positive cells were defined as apoptotic cells. Since honey shows both antioxidant activity and cytotoxicity at almost the same concentration, it can prevent the free radical induced cancer as prophylactic agent and kill the cancer cells by apoptotic process as a chemotherapeutic agent. Everyday intake of honey can prevent the cancer induction.

Keywords: anticancer, cells, DNA, honey

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Marah El-Beeli, Abdullah Balkhair, Zakaryia Al Muharmi, Samir Al Adawi, Mansoor Al-Jabri, Abdullah Al Rawahi, Hazaa Al Yahyae, Eman Al Balushi, Yahya M. Al-Farsi

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The health care service and the anticancer chemotherapeutics has changed the natural history of cancer into manageable chronic disease and improve the cancer patient’s lifestyle and increase the survival time. Despite that, still, infection is the major dilemma opposing the cancer patient either because of the clinical presentation of the cancer type and impaired immune system or as a consequence of anticancer therapy. This study has been conducted to1) track changes in the epidemiology of hospital-acquired bloodstream infections among patients with malignancies in the last five years. 2) To explore the causative pathogens and 3) the outcome of HA-BSIs in patients with a different types of malignancies. An ampi-directional study (retrospective and prospective follow up) of patients with malignancies admitted at Sultan Qaboos University hospital (570-bed tertiary hospital) during the study period (from January 2015 to December 2019). The cumulative frequency and prevalence rates of HA-BSIs by patients and isolates were calculated. In addition, the cumulative frequency of participants with single versus mixed infections and types of causative micro-organisms of HA-BSIs were obtained. A total of 1246 event of HA-BSIs has occurred during the study period. Nearly the third (30.25%) of the HA-BSI events was identified among 288 patients with malignancies. About 20% of cases were mixed infections (more than one isolate). Staphylococcus spp were the predominant isolated pathogen (24.7%), followed by Klebsiella spp (15.8%), Escherichia spp (13%), and Pseudomonas spp (9.3%). About half (51%) of cases died in the same year, and (64%) of the deaths occur within two weeks after the infection. According to the observations, no changes in the trends of epidemiology, causative pathogens, morbidity, and mortality rates in the last five years.

Keywords: epidemiology, haematological malignancies, hospital acquired bloodstream infections, solid malignancies

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Authors: Hawon Lee, Young-Pil Kim

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Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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Authors: Arianna Zhu, Thomas Bakupog

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Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

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Authors: Sean Hall

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Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

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Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Chiara Cosentino, Carlo Pruneti, Carla Merisio, Domenico Sgromo

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Introduction – Psychoneuroimmunology as approach clearly showed how psychological features can influence health through specific physiological pathways linked to the stress reaction. This can be true also in cancer, in its latter conceptualization seen as a chronic disease. Therefore, it is still not clear how the psychological features can combine with a physiological specific path, for a better adjustment to cancer. The aim of this study is identifying how in Italian survivors, perceived social support, body image, coping and quality of life correlate with or influence Heart Rate Variability (HRV), the physiological parameter that can mirror a condition of chronic stress or a good relaxing capability. Method - The study had an exploratory transversal design. The final sample was made of 38 ovarian cancer survivors aged from 29 to 80 (M= 56,08; SD=12,76) following a program for Ovarian Cancer at the Oncological Clinic, University Hospital of Parma, Italy. Participants were asked to fill: Multidimensional Scale of Perceived Social Support (MSPSS); Derridford Appearance Scale-59 (DAS-59); Mental Adjustment to Cancer (MAC); Quality of Life Questionnaire (EORTC). For each participant was recorded Short-Term HRV (5 minutes) using emWavePro. Results– Data showed many interesting correlations within the psychological features. EORTC scores have a significant correlation with DAS-59 (r =-.327 p <.05), MSPSS (r =.411 p<.05), and MAC scores, in particular with the strategy Fatalism (r =.364 p<.05). A good social support improves HRV (F(1,33)= 4.27 p<.05). Perceiving themselves as effective in their environment, preserving a good role functioning (EORTC), positively affects HRV (F(1,33)=9.810 p<.001). Women admitting concerns towards body image seem prone to emotive disclosure, reducing emotional distress and improving HRV (β=.453); emotional avoidance worsens HRV (β=-.391). Discussion and conclusion - Results showed a strong relationship between body image and Quality of Life. These data suggest that higher concerns on body image, in particular, the negative self-concept linked to appearance, was linked to the worst functioning in everyday life. The relation between the negative self-concept and a reduction in emotional functioning is understandable in terms of possible distress deriving from the perception of body appearance. The relationship between a high perceived social support and a better functioning in everyday life was also confirmed. In this sample fatalism, was associated with a better physical, role and emotional functioning. In these women, the presence of a good support may activate the physiological Social Engagement System improving their HRV. Perceiving themselves effective in their environment, preserving a good role functioning, also positively affects HRV, probably following the same physiological pathway. A higher presence of concerns about appearance contributes to a higher HRV. Probably women admitting more body concerns are prone to a better emotive disclosure. This could reduce emotional distress improving HRV and global health. This study reached preliminary demonstration of an ‘Integrated Model of Defense’ in these cancer survivors. In these model, psychological features interact building a better quality of life and a condition of psychological well-being that is associated and influence HRV, then the physiological condition.

Keywords: cancer survivors, heart rate variability, ovarian cancer, psychophysiological adjustment

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Jiri Kysucan, Dusan Klos, Katherine Vomackova, Pavel Koranda, Martin Lovecek, Cestmir Neoral, Roman Havlik

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Aim: The prognosis of patients with pancreatic cancer is poor. The median of survival after establishing diagnosis is 3-11 months without surgical treatment, 13-20 months with surgical treatment depending on the disease stage, 5-year survival is less than 5%. Radical surgical resection remains the only hope of curing the disease. Early diagnosis with valid establishment of tumor resectability is, therefore, the most important aim for patients with pancreatic cancer. The aim of the work is to evaluate the contribution and define the role of 18F-FDG PET/CT in preoperative staging. Material and Methods: In 195 patients (103 males, 92 females, median age 66,7 years, 32-88 years) with a suspect pancreatic lesion, as part of the standard preoperative staging, in addition to standard examination methods (ultrasonography, contrast spiral CT, endoscopic ultrasonography, endoscopic ultrasonographic biopsy), a hybrid 18F-FDG PET/CT was performed. All PET/CT findings were subsequently compared with standard staging (CT, EUS, EUS FNA), with peroperative findings and definitive histology in the operated patients as reference standards. Interpretation defined the extent of the tumor according to TNM classification. Limitations of resectability were local advancement (T4) and presence of distant metastases (M1). Results: PET/CT was performed in a total of 195 patients with a suspect pancreatic lesion. In 153 patients, pancreatic carcinoma was confirmed and of these patients, 72 were not indicated for radical surgical procedure due to local inoperability or generalization of the disease. The sensitivity of PET/CT in detecting the primary lesion was 92.2%, specificity was 90.5%. A false negative finding in 12 patients, a false positive finding was seen in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76,0%. In evaluating regional lymph nodes, sensitivity was 51.9%, specificity 58.3%, PPV 58,3%, NPV 51.9%. In detecting distant metastases, PET/CT reached a sensitivity of 82.8%, specificity was 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which were not detected by standard methods. In 15 patients (15.6%) with potentially radically resectable findings, the procedure was contraindicated based on PET/CT findings and the treatment strategy was changed. Conclusion: PET/CT is a highly sensitive and specific method useful in preoperative staging of pancreatic cancer. It improves the selection of patients for radical surgical procedures, who can benefit from it and decreases the number of incorrectly indicated operations.

Keywords: cancer, PET/CT, staging, surgery

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Ayush Shrivastava, Arpit Chaudhary, Devang Kulshreshtha, Vibhav Prakash Singh, Rajeev Srivastava

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Early diagnosis of breast cancer can improve the survival rate by detecting cancer at an early stage. Breast region segmentation is an essential step in the analysis of digital mammograms. Accurate image segmentation leads to better detection of cancer. It aims at separating out Region of Interest (ROI) from rest of the image. The procedure begins with removal of labels, annotations and tags from the mammographic image using morphological opening method. Pectoral Muscle Sliding Window Algorithm (PMSWA) is used for removal of pectoral muscle from mammograms which is necessary as the intensity values of pectoral muscles are similar to that of ROI which makes it difficult to separate out. After removing the pectoral muscle, Dispersed Region Growing Algorithm (DRGA) is used for segmentation of mammogram which disperses seeds in different regions instead of a single bright region. To demonstrate the validity of our segmentation method, 322 mammographic images from Mammographic Image Analysis Society (MIAS) database are used. The dataset contains medio-lateral oblique (MLO) view of mammograms. Experimental results on MIAS dataset show the effectiveness of our proposed method.

Keywords: CAD, dispersed region growing algorithm (DRGA), image segmentation, mammography, pectoral muscle sliding window algorithm (PMSWA)

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Authors: Loai AbdAllah, Mahmoud Kaiyal

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Missing values in real-world datasets are a common problem. Many algorithms were developed to deal with this problem, most of them replace the missing values with a fixed value that was computed based on the observed values. In our work, we used a distance function based on Bhattacharyya distance to measure the distance between objects with missing values. Bhattacharyya distance, which measures the similarity of two probability distributions. The proposed distance distinguishes between known and unknown values. Where the distance between two known values is the Mahalanobis distance. When, on the other hand, one of them is missing the distance is computed based on the distribution of the known values, for the coordinate that contains the missing value. This method was integrated with Wikaya, a digital health company developing a platform that helps to improve prevention of chronic diseases such as diabetes and cancer. In order for Wikaya’s recommendation system to work distance between users need to be measured. Since there are missing values in the collected data, there is a need to develop a distance function distances between incomplete users profiles. To evaluate the accuracy of the proposed distance function in reflecting the actual similarity between different objects, when some of them contain missing values, we integrated it within the framework of k nearest neighbors (kNN) classifier, since its computation is based only on the similarity between objects. To validate this, we ran the algorithm over diabetes and breast cancer datasets, standard benchmark datasets from the UCI repository. Our experiments show that kNN classifier using our proposed distance function outperforms the kNN using other existing methods.

Keywords: missing values, incomplete data, distance, incomplete diabetes data

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Selim M. Khan, Aaron A. Goodarzi, Joshua M. Taron, Tryggve Rönnqvist

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Indoor air quality, a prime determinant of health, is strongly influenced by the presence of hazardous radon gas within the built environment. As a health issue, dangerously high indoor radon arose within the 20th century to become the 2nd leading cause of lung cancer. While the 21st century building metrics and human behaviors have captured, contained, and concentrated radon to yet higher and more hazardous levels, the issue is rapidly worsening in Canada. It is established that Canadians in the Prairies are the 2nd highest radon-exposed population in the world, with 1 in 6 residences experiencing 0.2-6.5 millisieverts (mSv) radiation per week, whereas the Canadian Nuclear Safety Commission sets maximum 5-year occupational limits for atomic workplace exposure at only 20 mSv. This situation is also deteriorating over time within newer housing stocks containing higher levels of radon. Deep machine learning (LSTM) algorithms were applied to analyze multiple quantitative and qualitative features, determine the most important contributory factors, and predicted radon levels in the known past (1990-2020) and projected future (2021-2050). The findings showed gradual downwards patterns in Sweden, whereas it would continue to go from high to higher levels in Canada over time. The contributory factors found to be the basement porosity, roof insulation depthness, R-factor, and air dynamics of the indoor environment related to human window opening behaviour. Building codes must consider including these factors to ensure adequate indoor ventilation and healthy living that can prevent lung cancer in non-smokers.

Keywords: radon, building metrics, deep learning, LSTM prediction model, lung cancer, canada, sweden

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Authors: Iris W. A. Boot, Anke Wesselius, Maurice P. Zeegers

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Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus , thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. Individual dietary data were pooled from three cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose–response relationships (Model 1) were examined using a nonparametric test for trend. In total, 2,871 cases and 522,364 non-cases were included in the analyses. The present study showed an overall increased BC risk for high dietary vitamin D intake (HR: 1.14, 95% CI: 1.03-1.26). A similar increase BC risk with high vitamin D intake was observed among women and for the non-muscle invasive BC subtype, (HR: 1.41, 95% CI: 1.15-1.72, HR: 1.13, 95% CI: 1.01-1.27, respectively). High calcium intake decreased the BC risk among women (HR: 0.81, 95% CI: 0.67-0.97). A combined inverse effect on BC risk was observed for low vitamin D intake and high calcium intake (HR: 0.67, 95% CI: 0.48-0.93), while a positive effect was observed for high vitamin D intake in combination with low, moderate and high phosphorus (HR: 1.31, 95% CI: 1.09-1.59, HR: 1.17, 95% CI: 1.01-1.36, HR: 1.16, 95% CI: 1.03-1.31, respectively). Combining all nutrients showed a decreased BC risk for low vitamin D intake, high calcium and moderate phosphor intake (HR: 0.37, 95% CI: 0.18-0.75), and an increased BC risk for moderate intake of all the nutrients (HR: 1.18, 95% CI: 1.02-1.38), for high vitamin D and low calcium and phosphor intake (HR: 1.28, 95% CI: 1.01-1.62), and for moderate vitamin D and calcium and high phosphorus intake (HR: 1.27, 95% CI: 1.01-1.59). No significant dose-response analyses were observed. The findings of this study show an increased BC risk for high dietary vitamin D intake and a decreased risk for high calcium intake. Besides, the study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

Keywords: bladder cancer, nutritional oncology, pooled cohort analysis, vitamin D

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Bharti Arora, Michael Chen, Steven Lun

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Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare and aggressive subtype of urothelial carcinoma that usually presents at an advanced clinical stage, has a predilection for early metastatic potential and is associated with poor prognosis. The first reported case of PUC was in 1991 and approximately 100 cases were reported in the literature worldwide. We present a case of a 43 year old female presenting with a 3-month history of urgency and frequency. Failing medical management of her urinary symptoms with anticholinergic medication, she underwent a diagnostic cystoscopy which revealed an erythematous and indurated bladder. Bladder biopsies of these regions revealed plasmacytoid urothelial carcinoma. Pre-operative staging scans were clear of any metastatic disease and the patient subsequently underwent a radical cystectomy and pelvic clearance with the formation of ileal conduit for urinary diversion. Histology confirmed plasmacytoid urothelial carcinoma with involvement of right upper vagina and focally positive margins in soft tissue at right and left sides of bladder. She received adjuvant chemotherapy but passed away within a year from disease progression. PUC can present atypically and our case highlights the role of cystoscopy in patients with persistent urinary symptoms. By reviewing the literature on PUC, we aim to raise awareness and improve understanding of this rare bladder cancer subtype amongst urologists.

Keywords: urology, bladder cancer, plasmacytoid urothelial cancer, literature review

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Authors: Huang Wei-Yi

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Objective: This article explores the intensive care nursing experience of a lung cancer patient with pulmonary embolism who was placed on ECMO. Following a sudden change in the patient’s condition and a consensus reached during a family meeting, the decision was made to withdraw life-sustaining equipment and collaborate with the palliative care team. Methods: The nursing period was from October 20 to October 27, 2023. The author monitored physiological data, observed, provided direct care, conducted interviews, performed physical assessments, and reviewed medical records. Together with the critical care team and bypass personnel, a comprehensive assessment was conducted using Gordon's Eleven Functional Health Patterns to identify the patient’s health issues, which included pain related to lung cancer and invasive devices, fear of death due to sudden deterioration, and altered tissue perfusion related to hemodynamic instability. Results: The patient was admitted with fever, back pain, and painful urination. During hospitalization, the patient experienced sudden discomfort followed by cardiac arrest, requiring multiple CPR attempts and ECMO placement. A subsequent CT angiogram revealed a pulmonary embolism. The patient's condition was further complicated by severe pain due to compression fractures, and a diagnosis of terminal lung cancer was unexpectedly confirmed, leading to emotional distress and uncertainty about future treatment. Throughout the critical care process, ECMO was removed on October 24, stabilizing the patient’s body temperature between 36.5-37°C and maintaining a mean arterial pressure of 60-80 mmHg. Pain management, including Morphine 8mg in 0.9% N/S 100ml IV drip q6h PRN and Ultracet 37.5 mg/325 mg 1# PO q6h, kept the pain level below 3. The patient was transferred to the ward on October 27 and discharged home on October 30. Conclusion: During the care period, collaboration with the medical team and palliative care professionals was crucial. Adjustments to pain medication, symptom management, and lung cancer-targeted therapy improved the patient’s physical discomfort and pain levels. By applying the unique functions of nursing and the four principles of palliative care, positive encouragement was provided. Family members, along with social workers, clergy, psychologists, and nutritionists, participated in cross-disciplinary care, alleviating anxiety and fear. The consensus to withdraw ECMO and life-sustaining equipment enabled the patient and family to receive high-quality care and maintain autonomy in decision-making. A follow-up call on November 1 confirmed that the patient was emotionally stable, pain-free, and continuing with targeted lung cancer therapy.

Keywords: intensive care, lung cancer, pulmonary embolism, ECMO

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: Chao Hsing Yeh, Wei Chun Lin

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Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: M. L. Yeung

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With the surge of divorce rate and male cancer onset/death rates, the phenomenon of divorced wives in the facing cancer death of their ex-husbands is not uncommon in Hong Kong. Yet, there is a dearth of study on the experiences of bereaved-divorced wives in the Hong Kong cultural context. This project fills the knowledge gap by conducting a qualitative study for having interviewed four bereaved ex-wives, who returned to ex-husbands’ end-of-life caregiving and eventually grieved for the ex-spousal’s death. From the perspectives of attachment theory and disenfranchised grief in the Hong Kong cultural context, a ‘double-loss’ experience is found in which interviewees suffer from the first loss of divorce and the second loss of ex-husbands’ death. Traumatic childhood experiences, attachment needs, role ambiguity, unresolved emotions and unrecognized grief are found significant in their lived experiences which alert the ‘double-loss’ is worthy of attention. Extending a family-centered end-of-life and bereavement care services to divorced couples is called for, in which validation on the attachment needs, ex-couple reconciliation, and acknowledgement on the disenfranchised grief are essential for social work practice on this group of clienteles specifically in Hong Kong cultural context.

Keywords: changing family, disenfranchised grief, divorce, ex-spousal death, marriage

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Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

Abstract:

BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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Authors: Ľudmila Ballová, Slavomír Kurhajec, Eva Petrovová, Jarmila Eftimová

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Angiogenesis, a formation of new blood vessels from a pre-existing vasculature, plays an important role in pathologic processes such as the growth and metastasis of tumours. Tumours cannot grow beyond a few millimetres without blood supply from the newly formed blood vessels from the host tissue, a process called tumour-induced angiogenesis. The successful research of antiangiogenic treatment of cancer has focused on nutraceuticals with angiogenesis-modulating properties. Berberine, as a major active component of the bark of Phellodendron amurense Rupr., has shown antitumour activity by intervening into different steps of carcinogenesis. The influence of ethanolic extract of Phellodendron amurese bark on the angiogenesis was tested in vivo on chick chorioallantoic membrane (CAM). The irritancy of the CAM after the application of the crude bark extract dissolved in normal saline (10 mg/mL) was investigated on embryonic day 7. No significant signs of the irritancy, such as vasoconstriction, hyperaemia, haemorrhage or coagulation were observed which indicates the harmless character of the extract. A significant reduction in vessel sprouting and higher percentage of avascular zone was observed in the case of CAM treated with the extract in comparison with non-treated CAM (control), which is a proof of the antiangiogenic potential of the extract. These results could contribute to the development of novel drugs for the treatment of cancer or other diseases, in which angiogenesis plays a significant role.

Keywords: angiogenesis, berberine, chorioallantoic membrane, irritancy, phellodendron amurense

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Authors: Ali Hamza

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Accurate segmentation of breast ultrasound images is of paramount importance in enhancing the diagnostic capabilities of breast cancer detection. This study presents an approach utilizing the U-Net architecture for segmenting breast ultrasound images aimed at improving the accuracy and reliability of mass identification within the breast tissue. The proposed method encompasses a multi-stage process. Initially, preprocessing techniques are employed to refine image quality and diminish noise interference. Subsequently, the U-Net architecture, a deep learning convolutional neural network (CNN), is employed for pixel-wise segmentation of regions of interest corresponding to potential breast masses. The U-Net's distinctive architecture, characterized by a contracting and expansive pathway, enables accurate boundary delineation and detailed feature extraction. To evaluate the effectiveness of the proposed approach, an extensive dataset of breast ultrasound images is employed, encompassing diverse cases. Quantitative performance metrics such as the Dice coefficient, Jaccard index, sensitivity, specificity, and Hausdorff distance are employed to comprehensively assess the segmentation accuracy. Comparative analyses against traditional segmentation methods showcase the superiority of the U-Net architecture in capturing intricate details and accurately segmenting breast masses. The outcomes of this study emphasize the potential of the U-Net-based segmentation approach in bolstering breast ultrasound image analysis. The method's ability to reliably pinpoint mass boundaries holds promise for aiding radiologists in precise diagnosis and treatment planning. However, further validation and integration within clinical workflows are necessary to ascertain their practical clinical utility and facilitate seamless adoption by healthcare professionals. In conclusion, leveraging the U-Net architecture for breast ultrasound image segmentation showcases a robust framework that can significantly enhance diagnostic accuracy and advance the field of breast cancer detection. This approach represents a pivotal step towards empowering medical professionals with a more potent tool for early and accurate breast cancer diagnosis.

Keywords: mage segmentation, U-Net, deep learning, breast cancer detection, diagnostic accuracy, mass identification, convolutional neural network

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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