Search results for: Breast Cancer
1379 Intracellular Sphingosine-1-Phosphate Receptor 3 Contributes to Lung Tumor Cell Proliferation
Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino
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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer
Procedia PDF Downloads 1991378 Tumor Size and Lymph Node Metastasis Detection in Colon Cancer Patients Using MR Images
Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi
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Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis
Procedia PDF Downloads 571377 Preparation of Gramine Nanosuspension and Protective Effect of Gramine on Human Oral Cell Lines by Induction of Apoptosis
Authors: K. Suresh, R. Arunkumar
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The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension
Procedia PDF Downloads 4521376 Concordance between Biparametric MRI and Radical Prostatectomy Specimen in the Detection of Clinically Significant Prostate Cancer and Staging
Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai
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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology
Procedia PDF Downloads 661375 The Use of Urine Cytology in an Australian Regional Hospital Compared to International Guidelines
Authors: Jake Tempo, Stephen Brough
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Introduction and Objectives: Urine cytology has a role in the diagnosis of urothelial cancer when used alongside cystoscopy and imaging, according to the European Association of Urology guidelines. It also has a role in the surveillance post-treatment of urothelial carcinoma. Collecting and analysing urine cytology is costly and time-consuming. We investigated the use of urine cytology in an Australian regional hospital to determine whether clinicians are following international guidelines. Materials and Methods: We analysed all urine cytology requests performed in an Australian regional hospital between 1st January 2017 and 31st December 2018. We reviewed the indication for urine cytology and the patients’ case notes to determine whether urine cytology changed management. Results: During the two-year study period, 153 patients had urine cytology analysed for a variety of indications. In no cases did cytology change the outcome of patient management significantly. In total, 69 of 153 (41%) urine cytology requests were not supported by urological society guidelines. Fifty requests were for haematuria, and twenty requests were for urothelial cancer surveillance. Seven were analysed for follow-up from previous urological investigations. Nine samples were sent for ureteric obstruction of unknown origin. Conclusion: Urine cytology, even when positive, did not significantly change management for the investigation of potential urothelial cancer, and therefore, its use as a diagnostic tool for this purpose should be reconsidered. Many cytology tests are expensive, unnecessary, and not supported by urological society guidelines.Keywords: cytology, bladder cancer, urine, urothelial carcinoma
Procedia PDF Downloads 911374 Determination of Prostate Specific Membrane Antigen (PSMA) Based on Combination of Nanocomposite Fe3O4@Ag@JB303 and Magnetically Assisted Surface Enhanced Raman Spectroscopy (MA-SERS)
Authors: Zuzana Chaloupková, Zdeňka Marková, Václav Ranc, Radek Zbořil
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Prostate cancer is now one of the most serious oncological diseases in men with an incidence higher than that of all other solid tumors combined. Diagnosis of prostate cancer usually involves detection of related genes or detection of marker proteins, such as PSA. One of the new potential markers is PSMA (prostate specific membrane antigen). PSMA is a unique membrane bound glycoprotein, which is considerably overexpressed on prostate cancer as well as neovasculature of most of the solid tumors. Commonly applied methods for a detection of proteins include techniques based on immunochemical approaches, including ELISA and RIA. Magnetically assisted surface enhanced Raman spectroscopy (MA-SERS) can be considered as an interesting alternative to generally accepted approaches. This work describes a utilization of MA-SERS in a detection of PSMA in human blood. This analytical platform is based on magnetic nanocomposites Fe3O4@Ag, functionalized by a low-molecular selector labeled as JB303. The system allows isolating the marker from the complex sample using application of magnetic force. Detection of PSMA is than performed by SERS effect given by a presence of silver nanoparticles. This system allowed us to analyze PSMA in clinical samples with limits of detection lower than 1 ng/mL.Keywords: diagnosis, cancer, PSMA, MA-SERS, Ag nanoparticles
Procedia PDF Downloads 2281373 A Systematic Review on Communication and Relations between Health Care Professionals and Patients with Cancer in Outpatient Settings Matter
Authors: Anne Prip, Kirsten Alling Møller, Dorte Lisbet Nielsen, Mary Jarden, Marie-Helene Olsen, Anne Kjaergaard Danielsen
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Background: The development in cancer care has shifted towards shorter hospital stays and more outpatient treatment. Today, cancer care and treatment predominantly takes place in outpatient settings where encounters between patients and health care professionals are often brief. This development will probably continue internationally as the global cancer burden seems to be growing significantly. Furthermore, the number of patients who require ambulatory treatments such as chemotherapy is increasing. Focusing on the encounters between health care professionals and patients during oncology treatment has thus become increasingly important due to a growing trend in outpatient cancer management. Objective: The aim of the systematic review was to summarize the literature from the perspective of the patient, on experiences of and the need for communication and relationships with the health care professional during chemotherapy treatment in an outpatient setting. Method: The review was designed and carried out according to the PRISMA guidelines and PICO framework. The systematic search was conducted in Medline, CINAHL, The Cochrane Library and Joanna Briggs Institute Evidence Based Practice Database. Results: In all, 1174 studies were identified by literature search. After duplicates were removed, the remaining studies (n = 1053) were screened for inclusion. Nine studies were included; qualitative (n = 5) and quantitative (n = 4) as they met the inclusions criteria. The review identified that communication and relationships between health care professionals and patients were important for the patients’ ability to cope with cancer and also had an impact on patients’ satisfaction with care in the outpatient clinic. Furthermore, the review showed that hope and positivity was a need and strategy for patients with cancer and was facilitated by health care professionals. Finally, it revealed that outpatient clinic visits framed and influenced communication and relationships. Conclusions: This review identified the significance of communication and the relationships between patients and health care professionals in the outpatient setting as it supports patients’ ability to cope with cancer. The review showed the need for health care professionals to pay attention to the relational aspects of communication in an outpatient clinic as encounters are often brief. Furthermore, the review helps to specify which elements of the communication are central in the patient-health care professional interaction from the patients' perspective. Finally, it shows a need for more research to investigate which type of interaction and intervention would be the most effective in supporting patients’ coping during chemotherapy in an outpatient clinic.Keywords: ambulatory chemotherapy, communication, health care professional-patient relation, nurse-patient relation, outpatient care, systematic review
Procedia PDF Downloads 4261372 Development a Home-Hotel-Hospital-School Community-Based Palliative Care Model for Patients with Cancer in Suratthani, Thailand
Authors: Patcharaporn Sakulpong, Wiriya Phokhwang
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Background: Banpunrug (Love Sharing House) established in 2013 provides a community-based palliative care for patients with cancer from 7 provinces in southern Thailand. These patients come to receive outpatient chemotherapy and radiotherapy at Suratthani Cancer Hospital. They are poor and uneducated; they need an accommodation during their 30-45 day course of therapy. Methods: A community-participatory action research (PAR) was employed to establish a model of palliative care for patients with cancer. The participants included health care providers, community, and patients and families. The PAR process includes problem identification and need assessment, community and team establishment, field survey, organization founding, model of care planning, action and inquiry (PDCA), outcome evaluation, and model distribution. Results: The model of care at Banpunrug involves the concepts of HHHS model, in that Banpunrug is a Home for patients; patients live in a house comfortable like in a Hotel resource; the patients are given care and living facilities similarly to those in a Hospital; the house is a School for patients to learn how to take care themselves, how to live well with cancer, and most importantly how to prepare themselves for a good death. The house is also a humanized care school for health care providers. Banpunrug’s philosophy of care is based on friendship therapy, social and spiritual support, community partnership, patient-family centeredness, Live & Love sharing house, and holistic and humanized care. With this philosophy, the house is managed as a home of the patients and everyone involved; everything is costless for all eligible patients and their family members; all facilities and living expense are donated from benevolent people, friends, and community. Everyone, including patients and family, has a sense of belonging to the house and there is no authority between health care providers and the patients in the house. The house is situated in a temple and a community and supported by many local nonprofit organizations and healthcare facilities such as a health promotion hospital at sub-disctrict level and Suratthani Cancer Hospital. Village health volunteers and multi-professional health care volunteers have contributed not only appropriate care, but also knowledge and experience to develop a distinguishing HHHS community-based palliative care model for patients with cancer. Since its opening the house has been a home for more than 400 patients and 300 family members. It is also a model for many national and international healthcare organizations and providers, who come to visit and learn about palliative care in and by community. Conclusions: The success of this palliative care model comes from community involvement, multi-professional volunteers and distributions, and concepts of HHHS model. Banpunrug promotes a consistent care across the cancer trajectory independent of prognosis in order to strengthen a full integration of palliativeKeywords: community-based palliative care, model, participatory action research, patients with cancer
Procedia PDF Downloads 2671371 Electrochemical Biosensor Based on Chitosan-Gold Nanoparticles, Carbon Nanotubes for Detection of Ovarian Cancer Biomarker
Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi
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Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles
Procedia PDF Downloads 2861370 Relationship between Causes of Carcass Condemnation and Other Welfare Indicators Collected in Three Poultry Slaughterhouses
Authors: Sara Santos, Cristina Saraiva, Sónia Saraiva
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The objective of this study was to evaluate the welfare of reared broilers using scoring systems at the slaughterhouse. The welfare of broilers from 70 different flocks was assessed in three different slaughterhouses, regarding 373043 animals, although not in equal proportions in each slaughterhouse due to the difference in the amount of flocks slaughtered per day because of different company size. Twenty-one flocks were evaluated in slaughterhouse A (30%), thirty in slaughterhouse B (42,9%) and nineteen in slaughterhouse C (27,1%). The parameters evaluated were feather cleanness, foot pad dermatitis, hock burn, breast burn and causes of carcass condemnation. Feather cleanness was scored into three classes: 0=clean; 1=moderately dirty and 2=dirty feathers. Foot pad dermatitis, hock burn and breast ulcer were graded in three classes: 0=no lesions, 1=moderate lesions and 2=severe lesions. Causes of carcass condemnation were divided into emaciation, ascites, colour alteration and febrile state, arthritis, aerosaculitis, dermatitis, peritonitis, myositis, cellulitis, extensive trauma and technopathies as mechanical trauma, insufficient bleeding and deficient plucking. Broilers evaluated had a body weight ranging between 0,909kg and 2,588kg (median 1,522kg) and age between 25 days and 45 days (median 33 days). Rejection rate of flocks ranged between 0,1% and 10,48% (median 1,4029%) and footpad dermatitis total score between 2 and 197, resulting in 20 flocks presenting moderate lesions and 15 flocks with severe lesions. Moderate hock burn was associated with severe foot pad dermatitis and with breast burn. The associations between these lesions suggest that the development of contact dermatitis is caused by a common cause, the prolonged contact with litter of poor quality. In conclusion, contact dermatitis lesions, mostly foot pad dermatitis, feather hygiene conditions and rejection rate were the main restrictions of good welfare and considered important indicators for the follow-up on the farm conditions.Keywords: broiler, dermatitis, welfare, slaughterhouse
Procedia PDF Downloads 1351369 Malnutrition of the Cancer Patients under Chemotherapy and Influence of Learned Food Aversions
Authors: Hafsa Chergui
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Malnutrition is a very common problem for hospitalized patients in general but it happens most to those who have a chronic disease such as cancer. Learned food aversions are defined as aversions which form toward foods after their ingestion has been temporally paired with illness (nausea or emesis). Learned food aversion may exert a negative impact on nutritional status and quality of life. The present review evaluates the literature derived both from laboratory animals and humans. Also, a questionnaire has been filled by patients under chemotherapy to assess the level of food aversions. This study evaluated the current research for avoiding the formation of aversions to dietary items in 200 cancer patients treated with chemotherapy. A scapegoat food or beverage can be used just before treatment to reduce the incidence of treatment-related aversions to foods in the individual s usual diet. The goal of this work is to inform the nurses and dieticians because they play a vital role in the daily assessment of the patients' nutritional status. Being aware of all the causes of malnutrition may help to suggest solutions to improve the health condition of the patient and avoid severe malnutrition.Keywords: chemotherapy, oncology, food aversion, taste aversion
Procedia PDF Downloads 2951368 The Effect of Psychosocial, Behavioral and Disease Specific Characteristics on Health-Related Quality of Life after Primary Surgery for Colorectal Cancer: A Cross Sectional Study of a Regional Australian Population
Authors: Lakmali Anthony, Madeline Gillies
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Background: Colorectal cancer (CRC) is usually managed with surgical resection. Many of the outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO), such as Health-Related Quality of life (HRQoL), provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. HRQoL has previously been shown to be impacted by psychosocial, behavioral and disease-specific characteristics. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods: Consecutive patients who had resection of colorectal cancer in a single regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey instrument designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Demographic and disease-specific data were also collected via medical record review. Results: Forty-six patients completed the survey. Clinically significant levels of fear of recurrence as well as emotional distress, were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for CRC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL; however, the operative approach (laparoscopic vs. open) was associated with HRQoL for these patients. All psychosocial factors measured were associated with HRQoL, including cancer worry, emotional distress, body image and dispositional optimism. Conclusion: HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative colorectal cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.Keywords: surgery, colorectal, cancer, PRO, HRQoL
Procedia PDF Downloads 691367 High-Dose-Rate Brachytherapy for Cervical Cancer: The Effect of Total Reference Air Kerma on the Results of Single-Channel and Tri-Channel Applicators
Authors: Hossain A., Miah S., Ray P. K.
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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer
Procedia PDF Downloads 991366 Targeting the EphA2 Receptor Tyrosine Kinases in Melanoma Cancer, both in Humans and Dogs
Authors: Shabnam Abdi, Behzad Toosi
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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.Keywords: ephA2, targeting, melanoma, human, canine
Procedia PDF Downloads 591365 An Activatable Prodrug for the Treatment of Metastatic Tumors
Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim
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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence
Procedia PDF Downloads 4521364 The Role of High-Intensity Focused Ultrasound (HIFU) in the Treatment of Fibroadenomas: A Systematic Review
Authors: Ahmed Gonnah, Omar Masoud, Mohamed Abdel-Wahab, Ahmed ElMosalamy, Abdulrahman Al-Naseem
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Introduction: Fibroadenomas are solid, mobile, and non-tender benign breast lumps, with the highest prevalence amongst young women aged between 15 and 35. Symptoms can include discomfort, and they can become problematic, particularly when they enlarge, resulting in many referrals for biopsies, with fibroadenomas accounting for 30-75% of the cases. Diagnosis is based on triple assessment that involves a clinical examination, ultrasound imaging and mammography, as well as core needle biopsies. Current management includes observation for 6-12 months, with the indication of definitive surgery, in cases that are older than 35 years or with fibroadenoma persistence. Serious adverse effects of surgery might include nipple-areolar distortion, scarring and damage to the breast tissue, as well as the risks associated with surgery and anesthesia, making it a non-feasible option. Methods: A literature search was performed on the databases EMBASE. MEDLINE/PubMed, Google scholar and Ovid, for English language papers published between 1st of January 2000 and 17th of March 2021. A structured protocol was employed to devise a comprehensive search strategy with keywords and Boolean operators defined by the research question. The keywords used for the search were ‘HIFU’, ‘High-Intensity Focused Ultrasound’, ‘Fibroadenoma’, ‘Breast’, ‘Lesion’. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Recently, a thermal ablative technique, High Intensity Focused Ultrasound (HIFU), was found to be a safe, non-invasive, and technically successful alternative, having displayed promising outcomes in reducing the volume of fibroadenomas, pain experienced by patients, and the length of hospitalization. Quality of life improvement was also evidenced, exhibited by the disappearance of symptoms, and enhanced physical activity post-intervention, in addition to patients’ satisfaction with the cosmetic results and future recommendation of the procedure to other patients. Conclusion: Overall, HIFU is a well-tolerated treatment associated with a low risk of complications that can potentially include erythema, skin discoloration and bruising, with the majority of this self-resolving shortly after the procedure.Keywords: ultrasound, HIFU, breast, efficacy, side effects, fibroadenoma
Procedia PDF Downloads 2221363 Synthesis of Multi-Functional Iron Oxide Nanoparticles for Targeted Drug Delivery in Cancer Treatment
Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour
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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle
Procedia PDF Downloads 801362 Utility of Routine Colonoscopy in Acute Diverticulitis
Authors: Naya Masood, Russell Hodgson, Mark Tacey
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Purpose: Patients with acute diverticulitis (AD) have an increased risk of underlying colorectal cancer (CRC); however, those with uncomplicated AD may have the same underlying population risk. This study informs on an Australian AD population who were not routinely offered colonoscopic follow-up. Methods: A 2-year (July 2016 – June 2018) retrospective study of patients admitted with CT-confirmed acute diverticulitis was conducted. CT findings were categorised as ‘complicated’ and ‘uncomplicated’ and were correlated with the detection of cancer in subsequent colonoscopy or follow-up. Results: 67.7% (n=292) of 431 patients were seen to have had complicated AD on an abdominopelvic CT scan. Patients were complicated most commonly due to bowel wall thickening reported on CT (90.4%), perforation (20.2%), or an abscess (12%). Follow-up colonoscopic evaluation was conducted in 52.9% (n=228) of total cases of AD, out of which 156 suffered complicated AD and the rest uncomplicated. None of the uncomplicated AD patients in our cohort were found to have CRC. Of those with complicated AD, six were found to have CRC. Conclusion: The only CRC diagnoses were made in patients with complicated AD. Despite available evidence, a significant proportion of uncomplicated AD patients were still undergoing colonoscopy. There is scope to further safely decrease the number of colonoscopies performed in AD patients.Keywords: acute diverticulitis, colonoscopy, colorectal cancer, advanced adenoma, complicated diverticulitis
Procedia PDF Downloads 921361 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer
Authors: Elvin P. Chizenga, Heidi Abrahamse
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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy
Procedia PDF Downloads 1221360 Evaluation on Estrogenic Effects of Diisononyl Adipate (DiNA) on MCF-7 Human Breast Cancer Cell Lines
Authors: Shih-cheng Li, Ming-Yi Chung, Mei-Lien Chen
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Background: Plasticizers, such as phthalates and adipates, were substances added to a material that provided flexibility and durability to plastics such as polyvinyl chloride (PVC). Phthalates were generally recognized as an endocrine disrupter due to their estrogenic and anti-androgenic activities. Phthalates had the capacity to bind to estrogen receptors, and hence they might prolong menstrual cycles and increase the proportion of premature menopause. Recently, adipates such as di-2-ethylhexyl adipate (DEHA) and di-isononyl adipate (DiNA) had replaced phthalates and were now used for food packaging. Methods: MCF-7 cell lines were treated with di-2-ethylhexyl phthalate (DEHP), di- 2-ethylhexyl adipate (DEHA), or di-isononyl adipate (DiNA) (10-6 , 10-5 , and 10-4 mol/l), using 17β-estradiol (10-8 mol/l) as a positive control. After incubations of 24, 48, 72, and 96 hours, the cells were tested using the alamarBlue assay. Results: The alamarBlue assay revealed that cell proliferation significantly increased after treatments of DEHP and DEHA for 24 hours at a concentration of 10-6, 10-5, and 10-4 mol/l. After more than 48 hours, cell proliferations in DEHP at 10-6, 10-5, and 10-4 mol/l significantly decreased compared to the control group. Conclusions: The present study demonstrates that adipates, as well as phthalates, were capable of inducing cell proliferation. We further used MDA-MB-231 cell lines to confirm that the proliferation effect was generated through binding to estrogen receptors.Keywords: MCF-7, phthalate, adipate, endocrine disrupter
Procedia PDF Downloads 2941359 The Nurse Practitioner’s Role Functions in Multi-Specialist Team When Caring for a Metastatic Colon Cancer Patient with Acute Intestinal Obstruction
Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen
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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team
Procedia PDF Downloads 1141358 Synthesis of PVA/γ-Fe2O3 Used in Cancer Treatment by Hyperthermia
Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli
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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing
Procedia PDF Downloads 3011357 NS5ABP37 Inhibits Liver Cancer by Impeding Lipogenesis and Cholesterogenesis
Authors: Shenghu Feng, Jun Cheng
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The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress
Procedia PDF Downloads 1521356 Call-Back Laterality and Bilaterality: Possible Screening Mammography Quality Metrics
Authors: Samson Munn, Virginia H. Kim, Huija Chen, Sean Maldonado, Michelle Kim, Paul Koscheski, Babak N. Kalantari, Gregory Eckel, Albert Lee
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In terms of screening mammography quality, neither the portion of reports that advise call-back imaging that should be bilateral versus unilateral nor how much the unilateral call-backs may appropriately diverge from 50–50 (left versus right) is known. Many factors may affect detection laterality: display arrangement, reflections preferentially striking one display location, hanging protocols, seating positions with respect to others and displays, visual field cuts, health, etc. The call-back bilateral fraction may reflect radiologist experience (not in our data) or confidence level. Thus, laterality and bilaterality of call-backs advised in screening mammography reports could be worthy quality metrics. Here, laterality data did not reveal a concern until drilling down to individuals. Bilateral screening mammogram report recommendations by five breast imaging, attending radiologists at Harbor-UCLA Medical Center (Torrance, California) 9/1/15--8/31/16 and 9/1/16--8/31/17 were retrospectively reviewed. Recommended call-backs for bilateral versus unilateral, and for left versus right, findings were counted. Chi-square (χ²) statistic was applied. Year 1: of 2,665 bilateral screening mammograms, reports of 556 (20.9%) recommended call-back, of which 99 (17.8% of the 556) were for bilateral findings. Of the 457 unilateral recommendations, 222 (48.6%) regarded the left breast. Year 2: of 2,106 bilateral screening mammograms, reports of 439 (20.8%) recommended call-back, of which 65 (14.8% of the 439) were for bilateral findings. Of the 374 unilateral recommendations, 182 (48.7%) regarded the left breast. Individual ranges of call-backs that were bilateral were 13.2–23.3%, 10.2–22.5%, and 13.6–17.9%, by year(s) 1, 2, and 1+2, respectively; these ranges were unrelated to experience level; the two-year mean was 15.8% (SD=1.9%). The lowest χ² p value of the group's sidedness disparities years 1, 2, and 1+2 was > 0.4. Regarding four individual radiologists, the lowest p value was 0.42. However, the fifth radiologist disfavored the left, with p values of 0.21, 0.19, and 0.07, respectively; that radiologist had the greatest number of years of experience. There was a concerning, 93% likelihood that bias against left breast findings evidenced by one of our radiologists was not random. Notably, very soon after the period under review, he retired, presented with leukemia, and died. We call for research to be done, particularly by large departments with many radiologists, of two possible, new, quality metrics in screening mammography: laterality and bilaterality. (Images, patient outcomes, report validity, and radiologist psychological confidence levels were not assessed. No intervention nor subsequent data collection was conducted. This uncomplicated collection of data and simple appraisal were not designed, nor had there been any intention to develop or contribute, to generalizable knowledge (per U.S. DHHS 45 CFR, part 46)).Keywords: mammography, screening mammography, quality, quality metrics, laterality
Procedia PDF Downloads 1581355 Evaluation of the Heating Capability and in vitro Hemolysis of Nanosized MgxMn1-xFe2O4 (x = 0.3 and 0.4) Ferrites Prepared by Sol-gel Method
Authors: Laura Elena De León Prado, Dora Alicia Cortés Hernández, Javier Sánchez
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Among the different cancer treatments that are currently used, hyperthermia has a promising potential due to the multiple benefits that are obtained by this technique. In general terms, hyperthermia is a method that takes advantage of the sensitivity of cancer cells to heat, in order to damage or destroy them. Within the different ways of supplying heat to cancer cells and achieve their destruction or damage, the use of magnetic nanoparticles has attracted attention due to the capability of these particles to generate heat under the influence of an external magnetic field. In addition, these nanoparticles have a high surface area and sizes similar or even lower than biological entities, which allow their approaching and interaction with a specific region of interest. The most used magnetic nanoparticles for hyperthermia treatment are those based on iron oxides, mainly magnetite and maghemite, due to their biocompatibility, good magnetic properties and chemical stability. However, in order to fulfill more efficiently the requirements that demand the treatment of magnetic hyperthermia, there have been investigations using ferrites that incorporate different metallic ions, such as Mg, Mn, Co, Ca, Ni, Cu, Li, Gd, etc., in their structure. This paper reports the synthesis of nanosized MgxMn1-xFe2O4 (x = 0.3 and 0.4) ferrites by sol-gel method and their evaluation in terms of heating capability and in vitro hemolysis to determine the potential use of these nanoparticles as thermoseeds for the treatment of cancer by magnetic hyperthermia. It was possible to obtain ferrites with nanometric sizes, a single crystalline phase with an inverse spinel structure and a behavior near to that of superparamagnetic materials. Additionally, at concentrations of 10 mg of magnetic material per mL of water, it was possible to reach a temperature of approximately 45°C, which is within the range of temperatures used for the treatment of hyperthermia. The results of the in vitro hemolysis assay showed that, at the concentrations tested, these nanoparticles are non-hemolytic, as their percentage of hemolysis is close to zero. Therefore, these materials can be used as thermoseeds for the treatment of cancer by magnetic hyperthermia.Keywords: ferrites, heating capability, hemolysis, nanoparticles, sol-gel
Procedia PDF Downloads 3401354 Computational Investigation on Structural and Functional Impact of Oncogenes and Tumor Suppressor Genes on Cancer
Authors: Abdoulie K. Ceesay
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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)
Procedia PDF Downloads 841353 Evaluation of the Influence of Graphene Oxide on Spheroid and Monolayer Culture under Flow Conditions
Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka
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In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).Keywords: cytotoxicity, graphene oxide, monolayer, spheroid
Procedia PDF Downloads 1241352 The Benefits of a Totally Autologous Breast Reconstruction Technique Using Extended Latissimus Dorsi Flap with Lipo-Modelling: A Seven Years United Kingdom Tertiary Breast Unit Results
Authors: Wisam Ismail, Brendan Wooler, Penelope McManus
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Introduction: The public perception of implants has been damaged in the wake of recent negative publicity and increasingly we are finding patients wanting to avoid them. Planned lipo-modelling to enhance the volume of a Latissimus dorsi flap is a viable alternative to silicone implants and maintains a Totally Autologous Technique (TAT). Here we demonstrate that when compared to an Implant Assisted Technique (IAT), a TAT offers patients many benefits that offset the requirement of more operations initially, with reduced short and long term complications, reduced symmetrisation surgery and reduced revision rates. Methods. Data was collected prospectively over 7 years. The minimum follows up was 3 years. The technique was generally standardized in the hand of one surgeon. All flaps were extended LD flaps (ELD). Lipo-modelling was performed using standard techniques. Outcome measures were unplanned secondary procedures, complication rates, and contralateral symmetrisation surgery rates. Key Results Were: Lower complication rates in the TAT group (18.5% vs. 33.3%), despite higher radiotherapy rates (TAT=49%, IAT=36.8%), TAT was associated with lower subsequent symmetrisation rates (30.6% vs. 50.9%), IAT had a relative risk of 3.1 for subsequent unplanned procedure, Autologous patients required an average of 1.76 sessions of lipo-modelling, Conclusions: Using lipo-modelling to enable totally autologous LD reconstruction offers significant advantages over an implant assisted technique. We have shown a lower subsequent unplanned procedure rate, lower revision surgery, and less contralateral symmetrisation surgery. We anticipate that a TAT will be supported by patient satisfaction surveys and long-term patient-reported cosmetic outcome data and intended to study this.Keywords: breast, Latissimus dorsi, lipomodelling, reconstruction
Procedia PDF Downloads 3341351 The Incidence of Prostate Cancer in Previous Infected E. Coli Population
Authors: Andreea Molnar, Amalia Ardeljan, Lexi Frankel, Marissa Dallara, Brittany Nagel, Omar Rashid
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Background: Escherichia coli is a gram-negative, facultative anaerobic bacteria that belongs to the family Enterobacteriaceae and resides in the intestinal tracts of individuals. E.Coli has numerous strains grouped into serogroups and serotypes based on differences in antigens in their cell walls (somatic, or “O” antigens) and flagella (“H” antigens). More than 700 serotypes of E. coli have been identified. Although most strains of E. coli are harmless, a few strains, such as E. coli O157:H7 which produces Shiga toxin, can cause intestinal infection with symptoms of severe abdominal cramps, bloody diarrhea, and vomiting. Infection with E. Coli can lead to the development of systemic inflammation as the toxin exerts its effects. Chronic inflammation is now known to contribute to cancer development in several organs, including the prostate. The purpose of this study was to evaluate the correlation between E. Coli and the incidence of prostate cancer. Methods: Data collected in this cohort study was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate patients infected with E.Coli infection and prostate cancer using the International Classification of Disease (ICD-10 and ICD-9 codes). Permission to use the database was granted by Holy Cross Health, Fort Lauderdale for the purpose of academic research. Data analysis was conducted through the use of standard statistical methods. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 81, 037 patients after matching in both infected and control groups, respectively. The two groups were matched by Age Range and CCI score. The incidence of prostate cancer was 2.07% and 1,680 patients in the E. Coli group compared to 5.19% and 4,206 patients in the control group. The difference was statistically significant by a p-value p<2.2x10-16 with an Odds Ratio of 0.53 and a 95% CI. Based on the specific treatment for E.Coli, the infected group vs control group were matched again with a result of 31,696 patients in each group. 827 out of 31,696 (2.60%) patients with a prior E.coli infection and treated with antibiotics were compared to 1634 out of 31,696 (5.15%) patients with no history of E.coli infection (control) and received antibiotic treatment. Both populations subsequently developed prostate carcinoma. Results remained statistically significant (p<2.2x10-16), Odds Ratio=0.55 (95% CI 0.51-0.59). Conclusion: This retrospective study shows a statistically significant correlation between E.Coli infection and a decreased incidence of prostate cancer. Further evaluation is needed in order to identify the impact of E.Coli infection and prostate cancer development.Keywords: E. Coli, prostate cancer, protective, microbiology
Procedia PDF Downloads 2131350 Study of Relation between P53 and Mir-146a Rs2910164 Polymorphism in Cervical Lesion
Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand
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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism
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