Search results for: Breast Cancer
986 Shared Decision Making in Oropharyngeal Cancer: The Development of a Decision Aid for Resectable Oropharyngeal Carcinoma, a Mixed Methods Study
Authors: Anne N. Heirman, Lisette van der Molen, Richard Dirven, Gyorgi B. Halmos, Michiel W.M. van den Brekel
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Background: Due to the rising incidence of oropharyngeal squamous cell cancer (OPSCC), many patients are challenged with choosing between transoral(robotic) surgery and radiotherapy, with equal survival and oncological outcomes. Also, functional outcomes are of little difference over the years. With this study, the wants and needs of patients and caregivers are identified to develop a comprehensible patient decision aid (PDA). Methods: The development of this PDA is based on the International Patient Decision Aid Standards criteria. In phase 1, relevant literature was reviewed and compared to current counseling papers. We interviewed ten post-treatment patients and ten doctors from four head and neck centers in the Netherlands, which were transcribed verbatim and analyzed. With these results, the first draft of the PDA was developed. Phase 2 beholds testing the first draft for comprehensibility and usability. Phase 3 beholds testing for feasibility. After this phase, the final version of the PDA was developed. Results: All doctors and patients agreed a PDA was needed. Phase 1 showed that 50% of patients felt well-informed after standard care and 35% missed information about treatment possibilities. Side effects and functional outcomes were rated as the most important for decision-making. With this information, the first version was developed. Doctors and patients stated (phase 2) that they were satisfied with the comprehensibility and usability, but there was too much text. The PDA underwent text reduction revisions and got more graphics. After revisions, all doctors found the PDA feasible and would contribute to regular counseling. Patients were satisfied with the results and wished they would have seen it before their treatment. Conclusion: Decision-making for OPSCC should focus on differences in side-effects and functional outcomes. Patients and doctors found the PDA to be of great value. Future research will explore the benefits of the PDA in clinical practice.Keywords: head-and-neck oncology, oropharyngeal cancer, patient decision aid, development, shared decision making
Procedia PDF Downloads 137985 Change of Endocrine and Exocrine Insufficiency on Non-Diabetes Patients after Distal Pancreatectomy: A Nationwide Database Study
Authors: Jin-Ming Wu, Te-Wei Ho, Yu-Wen Tien
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Background: The aim of this population-based study was to determine the occurrence of diabetes and exocrine pancreatic insufficiencies (EPI) on non-diabetes subjects receiving distal pancreatectomy (DP). Method: A nationwide cohort study between 2000 and 2010 was collected from the Taiwan National Health Insurance Research Database. Among 3264 DP patients, we identified 1410 non-diabetes and 966 non-diabetes non-EPI. Results. Of 1410 non-diabetes DP subjects, 312 patients (22.1%) developed newly-diagnosed diabetes after PD. On a multiple logistic regression model, co-morbid hyperlipidemia (odds ratio, 1.640; 95% CI, 1.362–2.763; P < 0.001) and pancreatitis (odds ratio, 2.428; 95% CI, 1.889–3.121; P < 0.001) significantly contributed to higher incidences of diabetes after DP. Moreover, 380 subjects (39.3%) developed EPI, and pancreatic cancer is the statistically significant risk factor (odds ratio, 4.663; 95% CI, 2.108–6.085; P < 0.001). Conclusion: The patients with co-morbid hyperlipidemia and chronic pancreatitis had higher rates of newly-diagnosed diabetes after DP, moreover, pancreatic cancer subjects had higher rates of pancreatic exocrine insufficiency after DP. The clinicians should be alert to follow up glucose metabolism and clinical symptoms of fat intolerance for DP patients.Keywords: distal pancreatectomy, National database, diabetes, exocrine insufficiency
Procedia PDF Downloads 193984 Camptothecin Promotes ROS-Mediated G2/M Phase Cell Cycle Arrest, Resulting from Autophagy-Mediated Cytoprotection
Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim
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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species
Procedia PDF Downloads 428983 The Relationships among Self-Efficacy, Critical Thinking and Communication Skills Ability in Oncology Nurses for Cancer Immunotherapy in Taiwan
Authors: Yun-Hsiang Lee
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Cancer is the main cause of death worldwide. With advances in medical technology, immunotherapy, which is a newly developed advanced treatment, is currently a crucial cancer treatment option. For better quality cancer care, the ability to communicate and critical thinking plays a central role in clinical oncology settings. However, few studies have explored the impact of communication skills on immunotherapy-related issues and their related factors. This study was to (i) explore the current status of communication skill ability for immunotherapy-related issues, self-efficacy for immunotherapy-related care, and critical thinking ability; and (ii) identify factors related to communication skill ability. This is a cross-sectional study. Oncology nurses were recruited from the Taiwan Oncology Nursing Society, in which nurses came from different hospitals distributed across four major geographic regions (North, Center, South, East) of Taiwan. A total of 123 oncology nurses participated in this study. A set of questionnaires were used for collecting data. Communication skill ability for immunotherapy issues, self-efficacy for immunotherapy-related care, critical thinking ability, and background information were assessed in this survey. Independent T-test and one-way ANOVA were used to examine different levels of communication skill ability based on nurses having done oncology courses (yes vs. no) and education years (< 1 year, 1-3 years, and > 3 years), respectively. Spearman correlation was conducted to understand the relationships between communication skill ability and other variables. Among the 123 oncology nurses in the current study, the majority of them were female (98.4%), and most of them were employed at a hospital in the North (46.8%) of Taiwan. Most of them possessed a university degree (78.9%) and had at least 3 years of prior work experience (71.7%). Forty-three of the oncology nurses indicated in the survey that they had not received oncology nurses-related training. Those oncology nurses reported moderate to high levels of communication skill ability for immunotherapy issues (mean=4.24, SD=0.7, range 1-5). Nurses reported moderate levels of self-efficacy for immunotherapy-related care (mean=5.20, SD=1.98, range 0-10) and also had high levels of critical thinking ability (mean=4.76, SD=0.60, range 1-6). Oncology nurses who had received oncology training courses had significantly better communication skill ability than those who had not received oncology training. Oncology nurses who had higher work experience (1-3 years, or > 3 years) had significantly higher levels of communication skill ability for immunotherapy-related issues than those with lower work experience (<1 year). When those nurses reported better communication skill ability, they also had significantly better self-efficacy (r=.42, p<.01) and better critical thinking ability (r=.47, p<.01). Taken altogether, courses designed to improve communication skill ability for immunotherapy-related issues can make a significant impact in clinical settings. Communication skill ability for oncology nurses is the major factor associated with self-efficacy and critical thinking, especially for those with lower work experience (< 1 year).Keywords: communication skills, critical thinking, immunotherapy, oncology nurses, self-efficacy
Procedia PDF Downloads 97982 Mage Fusion Based Eye Tumor Detection
Authors: Ahmed Ashit
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Image fusion is a significant and efficient image processing method used for detecting different types of tumors. This method has been used as an effective combination technique for obtaining high quality images that combine anatomy and physiology of an organ. It is the main key in the huge biomedical machines for diagnosing cancer such as PET-CT machine. This thesis aims to develop an image analysis system for the detection of the eye tumor. Different image processing methods are used to extract the tumor and then mark it on the original image. The images are first smoothed using median filtering. The background of the image is subtracted, to be then added to the original, results in a brighter area of interest or tumor area. The images are adjusted in order to increase the intensity of their pixels which lead to clearer and brighter images. once the images are enhanced, the edges of the images are detected using canny operators results in a segmented image comprises only of the pupil and the tumor for the abnormal images, and the pupil only for the normal images that have no tumor. The images of normal and abnormal images are collected from two sources: “Miles Research” and “Eye Cancer”. The computerized experimental results show that the developed image fusion based eye tumor detection system is capable of detecting the eye tumor and segment it to be superimposed on the original image.Keywords: image fusion, eye tumor, canny operators, superimposed
Procedia PDF Downloads 359981 Network Based Molecular Profiling of Intracranial Ependymoma over Spinal Ependymoma
Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam
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Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.Keywords: systems biology, ependymoma, deg, network analysis
Procedia PDF Downloads 295980 Optimizing 3D Shape Parameters of Sports Bra Pads in Motion by Finite Element Dynamic Modelling with Inverse Problem Solution
Authors: Jiazhen Chen, Yue Sun, Joanne Yip, Kit-Lun Yick
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The design of sports bras poses a considerable challenge due to the difficulty in accurately predicting the wearing result after computer-aided design (CAD). It needs repeated physical try-on or virtual try-on to obtain a comfortable pressure range during motion. Specifically, in the context of running, the exact support area and force exerted on the breasts remain unclear. Consequently, obtaining an effective method to design the sports bra pads shape becomes particularly challenging. This predicament hinders the successful creation and production of sports bras that cater to women's health needs. The purpose of this study is to propose an effective method to obtain the 3D shape of sports bra pads and to understand the relationship between the supporting force and the 3D shape parameters of the pads. Firstly, the static 3D shape of the sports bra pad and human motion data (Running) are obtained by using the 3D scanner and advanced 4D scanning technology. The 3D shape of the sports bra pad is parameterised and simplified by Free-form Deformation (FFD). Then the sub-models of sports bra and human body are constructed by segmenting and meshing them with MSC Apex software. The material coefficient of sports bras is obtained by material testing. The Marc software is then utilised to establish a dynamic contact model between the human breast and the sports bra pad. To realise the reverse design of the sports bra pad, this contact model serves as a forward model for calculating the inverse problem. Based on the forward contact model, the inverse problem of the 3D shape parameters of the sports bra pad with the target bra-wearing pressure range as the boundary condition is solved. Finally, the credibility and accuracy of the simulation are validated by comparing the experimental results with the simulations by the FE model on the pressure distribution. On the one hand, this research allows for a more accurate understanding of the support area and force distribution on the breasts during running. On the other hand, this study can contribute to the customization of sports bra pads for different individuals. It can help to obtain sports bra pads with comfortable dynamic pressure.Keywords: sports bra design, breast motion, running, inverse problem, finite element dynamic model
Procedia PDF Downloads 50979 Pancreatic Adenocarcinoma Correctly Diagnosed by EUS but nor CT or MRI
Authors: Yousef Reda
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Pancreatic cancer has an overall dismal prognosis. CT, MRI and Endoscopic Ultrasound are most often used to establish the diagnosis. We present a case of a patient found on abdominal CT and MRI to have an 8 mm cystic lesion within the head of the pancreas which was thought to be a benign intraductal papillary mucinous neoplasm (IPMN). Further evaluation by EUS demonstrated a 1 cm predominantly solid mass that was proven to be an adenocarcinoma by EUS-guided FNA. The patient underwent a Whipple procedure. The final pathology confirmed a 1 cm pT1 N0 pancreatic ductal adenocarcinoma. Case: A 63-year-old male presented with left upper quadrant pain and an abdominal CT demonstrated an 8 mm lesion within the head of the pancreas that was thought to represent a side branch IPMN. An MRI also showed similar findings. Four months later due to ongoing symptoms an EUS was performed to re-evaluate the pancreatic lesion. EUS revealed a predominantly solid hypoechoic, homogeneous mass measuring 12 mm x 9 mm. EUS-guided FNA was performed and was positive for adenocarcinoma. The patient underwent a Whipple procedure that confirmed it to be a ductal adenocarcinoma, pT1N0. The solid mass was noted to be adjacent to a cystic dilation with no papillary architecture and scant epithelium. The differential diagnosis resided between cystic degeneration of a primary pancreatic adenocarcinoma versus malignant degeneration within a side-branch IPMN. Discussion: The reported sensitivity of CT for pancreatic cancer is approximately 90%. For pancreatic tumors, less than 3 cm the sensitivity of CT is reduced ranging from 67-77%. MRI does not significantly improve overall detection rates compared to CT. EUS, however is superior to CT in the detection of pancreatic cancer, in particular among lesions smaller than 3 cm. EUS also outperforms CT and MRI in distinguishing neoplastic from non-neoplastic cysts. In this case, both MRI and CT failed to detect a small pancreatic adenocarcinoma. The addition of EUS and FNA to abdominal imaging can increase overall accuracy for the diagnosis of neoplastic pancreatic lesions. It may be prudent that when small lesions although appearing as a benign IPMN should further be evaluated by EUS as this would lead to potentially identifying earlier stage pancreatic cancers and improve survival in a disease which has a dismal prognosis. Procedia PDF Downloads 257978 The Role of Txnrd2 Deficiency in Epithelial-to-Mesenchymal-Transition (EMT) and Tumor Formation in Pancreatic Cancer
Authors: Chao Wu
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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS
Procedia PDF Downloads 112977 TiO₂ Nanotube Array Based Selective Vapor Sensors for Breath Analysis
Authors: Arnab Hazra
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Breath analysis is a quick, noninvasive and inexpensive technique for disease diagnosis can be used on people of all ages without any risk. Only a limited number of volatile organic compounds (VOCs) can be associated with the occurrence of specific diseases. These VOCs can be considered as disease markers or breath markers. Selective detection with specific concentration of breath marker in exhaled human breath is required to detect a particular disease. For example, acetone (C₃H₆O), ethanol (C₂H₅OH), ethane (C₂H₆) etc. are the breath markers and abnormal concentrations of these VOCs in exhaled human breath indicates the diseases like diabetes mellitus, renal failure, breast cancer respectively. Nanomaterial-based vapor sensors are inexpensive, small and potential candidate for the detection of breath markers. In practical measurement, selectivity is the most crucial issue where trace detection of breath marker is needed to identify accurately in the presence of several interfering vapors and gases. Current article concerns a novel technique for selective and lower ppb level detection of breath markers at very low temperature based on TiO₂ nanotube array based vapor sensor devices. Highly ordered and oriented TiO₂ nanotube array was synthesized by electrochemical anodization of high purity tatinium (Ti) foil. 0.5 wt% NH₄F, ethylene glycol and 10 vol% H₂O was used as the electrolyte and anodization was carried out for 90 min with 40 V DC potential. Au/TiO₂ Nanotube/Ti, sandwich type sensor device was fabricated for the selective detection of VOCs in low concentration range. Initially, sensor was characterized where resistive and capacitive change of the sensor was recorded within the valid concentration range for individual breath markers (or organic vapors). Sensor resistance was decreased and sensor capacitance was increased with the increase of vapor concentration. Now, the ratio of resistive slope (mR) and capacitive slope (mC) provided a concentration independent constant term (M) for a particular vapor. For the detection of unknown vapor, ratio of resistive change and capacitive change at any concentration was same to the previously calculated constant term (M). After successful identification of the target vapor, concentration was calculated from the straight line behavior of resistance as a function of concentration. Current technique is suitable for the detection of particular vapor from a mixture of other interfering vapors.Keywords: breath marker, vapor sensors, selective detection, TiO₂ nanotube array
Procedia PDF Downloads 152976 Factors Associated with Seroconversion of Oral Polio Vaccine among the Children under 5 Year in District Mirpurkhas, Pakistan 2015
Authors: Muhammad Asif Syed, Mirza Amir Baig
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Background: Pakistan is one of the two remaining polio-endemic countries, posing a significant public health challenge for global polio eradication due to failure to interrupt polio transmission. Country specific seroprevalence studies help in the evaluation of immunization program performance, the susceptibility of population against polio virus and identification of existing level of immunity with factors that affect seroconversion of the oral polio vaccine (OPV). The objective of the study was to find out factors associated with seroconversion of the OPV among children 6-59 months in Pakistan. Methods: A Hospital based cross-sectional serosurvey was undertaken in May-June 2015 at District Mirpurkhas, Sindh-Pakistan. Total 180 children aged 6–59 months were selected by using systematic random sampling from Muhammad Medical College Hospital, Mirpurkhas. Demographic, vaccination history and risk factors information were collected from the parents/guardian. Blood sample was collected and tested for the detection of poliovirus IgG antibodies by using ELISA Kit. The IgG titer <10 IU/ml, 50 to <150 IU/ml and >150 IU/ml was defined as negative, weak positive and positive immunity respectively. Pearson Chi-square test was used to determine the difference in seroprevalence in univariate analysis. Results: A total of 180 subjects were enrolled mean age was 23 months (7 -59 months). Off these 160 (89%) children were well and 18 (10%) partially protected against polio virus. Two (1.1%) children had no protection against polio virus as they had <10 IU/ml poliovirus IgG antibodies titer. Both negative cases belong from the female gender, age group 12-23 months, urban area and BMI <50 percentile. There was a difference between normal and the wasting children; it did attain statistical significance (χ2= 35.5, p=0.00). The difference in seroconversion was also observed in relation to the gender (χ2=6.23, p=0.04), duration of breast feeding (χ2=18.6, p=0.04), history of diarrheal disease before polio vaccine administration (χ2=7.7, p=0.02), and stunting (χ2= 114, p=0.00). Conclusion: This study demonstrated that near 90% children achieve seroconversion of OPV and well protected against polio virus. There is an urgent need to focus on factors like duration of breast feeding, diarrheal diseases and malnutrition (acute and chronic) among the children as an immunization strategy.Keywords: seroconversion, oral polio vaccine, Polio, Pakistan
Procedia PDF Downloads 298975 Curative Role of Bromoenol Lactone, an Inhibitor of Phospholipase A2 Enzyme, during Cigarette Smoke Condensate Induced Anomalies in Lung Epithelium
Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja
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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone
Procedia PDF Downloads 179974 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade
Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam
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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.Keywords: adamantane, EGFR, HCC, apoptosis
Procedia PDF Downloads 141973 Surfactant Free Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatment
Authors: M. Sneha, N. Meenakshi Sundaram
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In recent times, magnetic hyperthermia is used for cancer treatment as a tool for active targeting of delivering drugs to the targeted site. It has a potential advantage over other heat treatment because there is no systemic buildup in organs and large doses are possible. The aim of this study is to develop a suitable magnetic biomaterial that can destroy the cancer cells as well as induce bone regeneration. In this work, the composite material was synthesized in two-steps. First, porous iron oxide nano needles were synthesized by hydrothermal process. Second, the hydroxyapatite, were synthesized from natural calcium (i.e., egg shell) and inorganic phosphorous source using wet chemical method. The crystalline nature is confirmed by powder X-ray diffraction analysis (XRD). Thermal analysis and the surface area of the material is studied by Thermo Gravimetric Analysis (TGA), Brunauer-Emmett and Teller (BET) technique. Scanning electron microscope (SEM) images show that the particles have nanoneedle-like morphology. The magnetic property is studied by vibrating sample magnetometer (VSM) technique which confirms the superparamagnetic behavior. This paper presents a simple and easy method for synthesis of magnetite/hydroxyapatite composites materials.Keywords: iron oxide nano needles, hydroxyapatite, superparamagnetic, hyperthermia
Procedia PDF Downloads 638972 The Effectiveness of Scalp Cooling Therapy on Reducing Chemotherapy Induced Alopecia: A Critical Literature Review
Authors: M. Krishna
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The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy
Procedia PDF Downloads 199971 Substantiate the Effects of Reactive Dyes and Aloe Vera on the Ultra Violet Protective Properties on Cotton Woven and Knitted Fabrics
Authors: Neha Singh
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The incidence of skin cancer has been rising worldwide due to excessive exposure to sun light. Climatic changes and depletion of ozone layer allow the easy entry of UV rays on earth, resulting skin damages such as sunburn, premature skin ageing, allergies and skin cancer. Researches have suggested many modes for protection of human skin against ultraviolet radiation; avoidance to outdoor activities, using textiles for covering the skin, sunscreen and sun glasses. However, this paper gives an insight about how textile material specially woven and knitted cotton can be efficiently utilized for protecting human skin from the harmful ultraviolet radiations by combining reactive dyes with Aloe Vera. Selection of the fabric was based on their utility and suitability as per the climate condition of the country for the upper and lower garment. A standard dyeing process was used, and Aloe Vera molecules were applied by in-micro encapsulation technique. After combining vat dyes with Aloe Vera excellent UPF (Ultra violet Protective Factor) was observed. There is a significant change in the UPF of vat dyed cotton fabric after treatment with Aloe Vera.Keywords: UV protection, aloe vera, protective clothing, reactive dyes, cotton, woven and knits
Procedia PDF Downloads 248970 Aboriginal Head and Neck Cancer Patients Have Different Patterns of Metastatic Involvement, and Have More Advanced Disease at Diagnosis
Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern
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Introduction: The mortality gap in Aboriginal Head and Neck Cancer is well known, but the reasons for poorer survival are not well established. Aim: We aimed to evaluate the locoregional and metastatic involvement, and stage at diagnosis, in Aboriginal compared with non-Aboriginal patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, regions involved, stage at diagnosis, treatment history, and survival and relapse patterns, including sites of metastatic and locoregional involvement. Results: Aboriginal patients had a significantly higher incidence of lung metastases (26.3% versus 13.7%, p=0.009). Aboriginal patients also had a numerically but non-statistically significant higher incidence of thoracic nodal involvement (10% vs 5.8%) and malignant pleural effusions (3.8% vs 2.5%). Aboriginal patients also had a numerically but not statistically significantly higher incidence of adrenal and bony involvement. Interestingly, non-Aboriginal patients had an increased rate of cutaneous (2.1% vs 0%) and liver metastases (4.6% vs 2.5%) compared with Aboriginal patients. In terms of locoregional involvement, Aboriginal patients were more than twice as likely to have contralateral neck involvement (58.8% vs 24.2%, p<0.00001), and 30% more likely to have ipsilateral neck lymph node involvement (78.8% vs 60%, p=0.002) than non-Aboriginal patients. Aboriginal patients had significantly more advanced disease at diagnosis (p=0.008). Aboriginal compared with non-Aboriginal patients were less likely to present with stage I (7.5% vs 22.5%), stage II (11.3% vs 13.8%), or stage III disease (13.8% vs 17.1%), and more likely to present with more advanced stage IVA (42.5% vs 34.6%), stage IVB (15% vs 7.1%), or stage IVC (10% vs 5%) disease (p=0.008). Number of regions of disease involvement was higher in Aboriginal patients (median 3, mean 3.64, range 1-10) compared with non-Aboriginal patients (median 2, mean 2.80, range 1-12). Conclusion: Aboriginal patients had a significantly higher incidence of lung metastases, and significantly more frequent involvement of ipsilateral and contralateral neck lymph nodes. Aboriginal patients also had significantly more advanced disease at presentation with a higher stage at diagnosis. We are performing further analyses to investigate explanations for these findings.Keywords: head and neck cancer, Aboriginal, metastases, locoregional, pattern of relapse, sites of disease
Procedia PDF Downloads 63969 Traditional Medicine and Islamic Holistic Approach in Palliative Care Management of Terminal Illpatient of Cancer
Authors: Mohammed Khalil Ur Rahman, Mohammed Alsharon, Arshad Muktar, Zahid Shaik
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Any ailment can go into terminal stages, cancer being one such disease which is many times detected in latent stages. Cancer is often characterized by constitutional symptoms which are agonizing in nature which disturbs patients and their family as well. In order to relieve such intolerable symptoms treatment modality employed is known to be ‘Palliative Care’. The goal of palliative care is to enhance patient’s quality of life by relieving or rather reducing the distressing symptoms of patients such as pain, nausea/ vomiting, anorexia/loss of appetite, excessive salivation, mouth ulcers, weight loss, constipation, oral thrush, emaciation etc. which are due to the effect of disease or due to the undergoing treatment such as chemotherapy, radiation etc. Ayurveda and Unani as well as other traditional medicines is getting more and more international attention in recent years and Ayurveda and Unani holistic perspective of the disease, it seems that there are many herbs and herbomineral preparation which can be employed in the treatment of malignancy and also in palliative care. Though many of them have yet to be scientifically proved as anti-cancerous but there is definitely a positive lead that some of these medications relieve the agonising symptoms thereby making life of the patient easy. Health is viewed in Islam in a holistic way. One of the names of the Quran is al-shifa' meaning ‘that which heals’ or ‘the restorer of health’ to refer to spiritual, intellectual, psychological, and physical health. The general aim of medical science, according to Islam, is to secure and adopt suitable measures which, with Allah’s permission, help to preserve or restore the health of the human body. Islam motivates the Physician to view the patient as one organism. The patient has physical, social, psychological, and spiritual dimensions that must be considered in synthesis with an integrated, holistic approach. Aims & Objectives: - To suggest herbs which are mentioned in Ayurveda Unani with potential palliative activity in case of Cancer patients. - Most of tibb nabawi [Prophetic Medicine] is preventive medicine and must have been divinely inspired. - Spiritual Aspects of Healing: Prayer, dua, recitation of the Quran - Remembrance of Allah play a central role.Materials & Method: Literary review of the herbs supported with experiential evidence will be discussed. Discussion: On the basis of collected data subject will be discussed in length. Conclusion: Will be presented in paper.Keywords: palliative care, holistic, Ayurvedic and Unani traditional system of medicine, Quran, hadith
Procedia PDF Downloads 337968 Intensive Crosstalk between Autophagy and Intracellular Signaling Regulates Osteosarcoma Cell Survival Response under Cisplatin Stress
Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury
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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.Keywords: JNK, autophagy, drug resistance, cancer
Procedia PDF Downloads 283967 Understanding Nanocarrier Efficacy in Drug Delivery Systems Using Molecular Dynamics
Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah
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Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier
Procedia PDF Downloads 288966 Encapsulation of Satureja khuzestanica Essential Oil in Chitosan Nanoparticles with Enhanced Antifungal Activity
Authors: Amir Amiri, Naghmeh Morakabati
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During the recent years the six-fold growth of cancer in Iran has led the production of healthy products to become a challenge in the food industry. Due to the young population in the country, the consumption of fast foods is growing. The chemical cancer-causing preservatives are used to produce these products more than the standard; so using an appropriate alternative seems to be important. On the one hand, the plant essential oils show the high antimicrobial potential against pathogenic and spoilage microorganisms and on the other hand they are highly volatile and decomposed under the processing conditions. The study aims to produce the loaded chitosan nanoparticles with different concentrations of savory essential oil to improve the anti-microbial property and increase the resistance of essential oil to oxygen and heat. The encapsulation efficiency was obtained in the range of 32.07% to 39.93% and the particle size distribution of the samples was observed in the range of 159 to 210 nm. The range of Zeta potential was obtained between -11.9 to -23.1 mV. The essential oil loaded in chitosan showed stronger antifungal activity against Rhizopus stolonifer. The results showed that the antioxidant property is directly related to the concentration of loaded essential oil so that the antioxidant property increases by increasing the concentration of essential oil. In general, it seems that the savory essential oil loaded in chitosan particles can be used as a food processor.Keywords: chitosan, encapsulation, essential oil, nanogel
Procedia PDF Downloads 264965 The Influence of Nutritional and Immunological Status on the Prognosis of Head and Neck Cancer
Authors: Ching-Yi Yiu, Hui-Chen Hsu
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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35%, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.
Procedia PDF Downloads 75964 Investigation of The Effects of Hydroxytyrosol on Cytotoxicity, Apoptosis, PI3K/Akt, and ERK 1/2 Pathways in Ovarian Cancer Cell Cultures
Authors: Latife Merve Oktay, Berrin Tugrul
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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer
Procedia PDF Downloads 352963 Comprehensive Care and the Right to Autonomy of Children and Adolescents with Cancer
Authors: Sandra Soca Lozano, Teresa Isabel Lozano Pérez, Germain Weber
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Cancer is a chronic disease of high prevalence in children and adolescents. Medical care in Cuba is carried out by a multidisciplinary team and family is the mediator between this team and the patient. Around this disease, there are interwoven many stereotypes and taboos by its relation to death. In this research report, we describe the work paradigm of psychological care to patients suffering from these diseases in the University Pediatric Hospital Juan Manuel Márquez of Havana, Cuba. We present the psychosocial factors that must be taken into account to provide comprehensive care and ensuring the quality of life of patients and their families. We also present the factors related to the health team and the management of information done with the patient. This is a descriptive proposal from the working experience accumulated in the named institution and in the review of the literature. As a result of this report we make a proposal of teamwork and the aspects in which psychological intervention should be continue performing in terms of increasing the quality of the care made by the health team. We conclude that it is necessary to continue improving the information management of children and adolescents with theses health problems and took into account their right to autonomy.Keywords: comprehensive care, management of information, psychosocial factors, right to autonomy
Procedia PDF Downloads 328962 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.
Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani
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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.
Procedia PDF Downloads 344961 Lipid-Coated Magnetic Nanoparticles for Frequency Triggered Drug Delivery
Authors: Yogita Patil-Sen
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Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)
Procedia PDF Downloads 228960 Cytotoxic Effect of Biologically Transformed Propolis on HCT-116 Human Colon Cancer Cells
Authors: N. Selvi Gunel, L. M. Oktay, H. Memmedov, B. Durmaz, H. Kalkan Yildirim, E. Yildirim Sozmen
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Object: Propolis which consists of compounds that are accepted as antioxidant, antimicrobial, antiseptic, antibacterial, anti-inflammatory, anti-mutagenic, immune-modulator and cytotoxic, is frequently used in current therapeutic applications. However, some of them result in allergic side effects, causing consumption to be restricted. Previously our group has succeeded in producing a new biotechnological product which was less allergenic. In this study, we purpose to optimize production conditions of this biologically-transformed propolis and determine the cytotoxic effects of obtained new products on colon cancer cell line (HCT-116). Method: Firstly, solid propolis samples were dissolved in water after weighing, grinding and sizing (sieve-35mesh) and applied 40 kHz/10 min ultrasonication. Samples were prepared according to inoculation with Lactobacillus plantarum in two different proportions (2.5% and 3.5%). Chromatographic analyzes of propolis were performed by UPLC-MS/MS (Waters, Milford, MA) system. Results were analysed by UPLC-MS/MS system MassLynx™ 4.1 software. HCT-116 cells were treated with propolis examples at 25-1000 µg/ml concentrations and cytotoxicity were measured by using WST-8 assay at 24, 48, and 72 hours. Samples with biological transformation were compared with the non-transformed control group samples. Our experiment groups were formed as follows: untreated (group 1), propolis dissolved in water ultrasonicated at 40 kHz/10 min (group 2), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 2.5% L. plantarum L1 strain (group 3), propolis dissolved in water ultrasonicated at 40 kHz/10 min and inoculated 3.5% L. plantarum L3 strain (group 4). Obtained data were calculated with Graphpad Software V5 and analyzed by two-way ANOVA test followed by Bonferroni test. Result: As a result of our study, the cytotoxic effect of propolis samples on HCT-116 cells was evaluated. There was a 7.21 fold increase in group 3 compared to group 2 in the concentration of 1000 µg/ml, and it was a 6.66 fold increase in group 3 compared to group 1 at the end of 24 hours. At the end of 48 hours, in the concentration of 500 µg/ml, it was determined 4.7 fold increase in group 4 compared to group 3. At the same time, in the concentration of 750 µg/ml it was determined 2.01 fold increase in group 4 compared to group 3 and in the same concentration, it was determined 3.1 fold increase in group 4 compared to group 2. Also, at the 72 hours, in the concentration of 750 µg/ml, it was determined 2.42 fold increase in group 3 according to group 2 and in the same time, in the concentration of 1000 µg/ml, it was determined 2.13 fold increase in group 4 according to group 2. According to cytotoxicity results, the group which were ultrasonicated at 40 kHz/10min and inoculated 3.5% L. plantarum L3-strain had a higher cytotoxic effect. Conclusion: It is known that bioavailability of propolis is halved in six months. The data obtained from our results indicated that biologically-transformed propolis had more cytotoxic effect than non-transformed group on colon cancer cells. Consequently, we suggested that L. plantarum-transformation provides both reduction of allergenicity and extension of bioavailability period by enhancing healthful polyphenols.Keywords: bio-transformation, propolis, colon cancer, cytotoxicity
Procedia PDF Downloads 129959 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis
Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini
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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry
Procedia PDF Downloads 146958 Isolation and Characterization of Anti-melanoma (Skin Cancer) Compounds from Corchorus olitorius .L
Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh
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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.Keywords: corchorus olitorius, melanoma, drug development, strophanthidin
Procedia PDF Downloads 127957 Effects of Cell Phone Electromagnetic Radiation on the Brain System
Authors: A. Alao Olumuyiwa
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Health hazards reported to be associated with exposure to electromagnetic radiations which include brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are discussed under a closed tabular model in this study. This review however showed that there is strong and robust evidence that chronic exposures to electromagnetic frequency across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, may result in brain cancer and other carcinogenic disease symptoms. There is therefore no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone has induced effects upon the blood –brain barrier permeability and the cerebellum exposure to continuous long hours RF radiation may result in significant increase in albumin extravasations. A physical Biomodeling approach is however employed to review this health effects using Specific Absorption Rate (SAR) of different GSM machines to critically examine the symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions in a variety of animal spices in classified grouped and sub grouped models.Keywords: brain cancer, electromagnetic radiations, physical biomodeling, specific absorption rate (SAR)
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