Search results for: cancer cell type
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 11291

Search results for: cancer cell type

9521 Piled Critical Size Bone-Biomimetic and Biominerizable Nanocomposites: Formation of Bioreactor-Induced Stem Cell Gradients under Perfusion and Compression

Authors: W. Baumgartner, M. Welti, N. Hild, S. C. Hess, W. J. Stark, G. Meier Bürgisser, P. Giovanoli, J. Buschmann

Abstract:

Perfusion bioreactors are used to solve problems in tissue engineering in terms of sufficient nutrient and oxygen supply. Such problems especially occur in critical size grafts because vascularization is often too slow after implantation ending up in necrotic cores. Biominerizable and biocompatible nanocomposite materials are attractive and suitable scaffold materials for bone tissue engineering because they offer mineral components in organic carriers – mimicking natural bone tissue. In addition, human adipose derived stem cells (ASCs) can potentially be used to increase bone healing as they are capable of differentiating towards osteoblasts or endothelial cells among others. In the present study, electrospun nanocomposite disks of poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/a-CaP) were seeded with human ASCs and eight disks were stacked in a bioreactor running with normal culture medium (no differentiation supplements). Under continuous perfusion and uniaxial cyclic compression, load-displacement curves as a function of time were assessed. Stiffness and energy dissipation were recorded. Moreover, stem cell densities in the layers of the piled scaffold were determined as well as their morphologies and differentiation status (endothelial cell differentiation, chondrogenesis and osteogenesis). While the stiffness of the cell free constructs increased over time caused by the transformation of the a-CaP nanoparticles into flake-like apatite, ASC-seeded constructs showed a constant stiffness. Stem cell density gradients were histologically determined with a linear increase in the flow direction from the bottom to the top of the 3.5 mm high pile (r2 > 0.95). Cell morphology was influenced by the flow rate, with stem cells getting more roundish at higher flow rates. Less than 1 % osteogenesis was found upon osteopontin immunostaining at the end of the experiment (9 days), while no endothelial cell differentiation and no chondrogenesis was triggered under these conditions. All ASCs had mainly remained in their original pluripotent status within this time frame. In summary, we have fabricated a critical size bone graft based on a biominerizable bone-biomimetic nanocomposite with preserved stiffness when seeded with human ASCs. The special feature of this bone graft was that ASC densities inside the piled construct varied with a linear gradient, which is a good starting point for tissue engineering interfaces such as bone-cartilage where the bone tissue is cell rich while the cartilage exhibits low cell densities. As such, this tissue-engineered graft may act as a bone-cartilage interface after the corresponding differentiation of the ASCs.

Keywords: bioreactor, bone, cartilage, nanocomposite, stem cell gradient

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9520 Globally Attractive Mild Solutions for Non-Local in Time Subdiffusion Equations of Neutral Type

Authors: Jorge Gonzalez Camus, Carlos Lizama

Abstract:

In this work is proved the existence of at least one globally attractive mild solution to the Cauchy problem, for fractional evolution equation of neutral type, involving the fractional derivate in Caputo sense. An almost sectorial operator on a Banach space X and a kernel belonging to a large class appears in the equation, which covers many relevant cases from physics applications, in particular, the important case of time - fractional evolution equations of neutral type. The main tool used in this work was the Hausdorff measure of noncompactness and fixed point theorems, specifically Darbo-type. Initially, the equation is a Cauchy problem, involving a fractional derivate in Caputo sense. Then, is formulated the equivalent integral version, and defining a convenient functional, using the analytic integral resolvent operator, and verifying the hypothesis of the fixed point theorem of Darbo type, give us the existence of mild solution for the initial problem. Furthermore, each mild solution is globally attractive, a property that is desired in asymptotic behavior for that solution.

Keywords: attractive mild solutions, integral Volterra equations, neutral type equations, non-local in time equations

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9519 Caffeic Acid Methyl and Ethyl Esters Exhibit Beneficial Effect on Glucose and Lipid Metabolism in Cultured Murine Insulin-Sensitive Cells

Authors: Hoda M. Eid, Abir Nachar, Farah Thong, Gary Sweeney, Pierre S. Haddad

Abstract:

Caffeic acid methyl ester (CAME) and caffeic ethyl esters (CAEE) were previously reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells via insulin-independent mechanisms involving the activation of adenosine monophosphate-activated protein kinase (AMPK). In the present study, we investigated the effect of the two compounds on the translocation of glucose transporter GLUT4 in L6 skeletal muscle cells. The cells were treated with the optimum non-toxic concentration (50 µM) of either CAME or CAEE for 18 h. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on GLUT1 and GLUT4 protein content were also measured by western immunoblot. Our results show that CAME and CAEE significantly increased glucose uptake, GLUT4 translocation and GLUT4 protein content. Furthermore, the effect of the two CA esters on two insulin-sensitive cell lines: H4IIE rat hepatoma and 3T3-L1 adipocytes were investigated. CAME and CAEE reduced the enzymatic activity of the key hepatic gluconeogenic enzyme glucose-6-phosphatase in a concentration-dependent manner. In addition, they exerted a concentration-dependent antiadipogenic effect on 3T3-L1 cells. Mitotic clonal expansion (MCE), a prerequisite for adipocytes differentiation was also concentration-dependently inhibited. The two compounds abrogated lipid droplet accumulation, blocked MCE and maintained cells in fibroblast-like state when applied at the maximum non-toxic concentration (100 µM). In addition, the expression of the early key adipogenic transcription factors CCAAT enhancer-binding protein beta (C/EBP-β) and the master regulator of adipogenesis peroxisome-proliferator-activated receptor gamma (PPAR-γ) were inhibited. We, therefore, conclude that CAME and CAEE exert pleiotropic benefits in several insulin-sensitive cell lines through insulin-independent mechanisms involving AMPK, hence they may treat obesity, diabetes and other metabolic diseases.

Keywords: type 2 diabetes mellitus, insulin resistance, GLUT4, Akt, AMPK.

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9518 Automated Computer-Vision Analysis Pipeline of Calcium Imaging Neuronal Network Activity Data

Authors: David Oluigbo, Erik Hemberg, Nathan Shwatal, Wenqi Ding, Yin Yuan, Susanna Mierau

Abstract:

Introduction: Calcium imaging is an established technique in neuroscience research for detecting activity in neural networks. Bursts of action potentials in neurons lead to transient increases in intracellular calcium visualized with fluorescent indicators. Manual identification of cell bodies and their contours by experts typically takes 10-20 minutes per calcium imaging recording. Our aim, therefore, was to design an automated pipeline to facilitate and optimize calcium imaging data analysis. Our pipeline aims to accelerate cell body and contour identification and production of graphical representations reflecting changes in neuronal calcium-based fluorescence. Methods: We created a Python-based pipeline that uses OpenCV (a computer vision Python package) to accurately (1) detect neuron contours, (2) extract the mean fluorescence within the contour, and (3) identify transient changes in the fluorescence due to neuronal activity. The pipeline consisted of 3 Python scripts that could both be easily accessed through a Python Jupyter notebook. In total, we tested this pipeline on ten separate calcium imaging datasets from murine dissociate cortical cultures. We next compared our automated pipeline outputs with the outputs of manually labeled data for neuronal cell location and corresponding fluorescent times series generated by an expert neuroscientist. Results: Our results show that our automated pipeline efficiently pinpoints neuronal cell body location and neuronal contours and provides a graphical representation of neural network metrics accurately reflecting changes in neuronal calcium-based fluorescence. The pipeline detected the shape, area, and location of most neuronal cell body contours by using binary thresholding and grayscale image conversion to allow computer vision to better distinguish between cells and non-cells. Its results were also comparable to manually analyzed results but with significantly reduced result acquisition times of 2-5 minutes per recording versus 10-20 minutes per recording. Based on these findings, our next step is to precisely measure the specificity and sensitivity of the automated pipeline’s cell body and contour detection to extract more robust neural network metrics and dynamics. Conclusion: Our Python-based pipeline performed automated computer vision-based analysis of calcium image recordings from neuronal cell bodies in neuronal cell cultures. Our new goal is to improve cell body and contour detection to produce more robust, accurate neural network metrics and dynamic graphs.

Keywords: calcium imaging, computer vision, neural activity, neural networks

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9517 Mobile Traffic Management in Congested Cells using Fuzzy Logic

Authors: A. A. Balkhi, G. M. Mir, Javid A. Sheikh

Abstract:

To cater the demands of increasing traffic with new applications the cellular mobile networks face new changes in deployment in infrastructure for making cellular networks heterogeneous. To reduce overhead processing the densely deployed cells require smart behavior with self-organizing capabilities with high adaptation to the neighborhood. We propose self-organization of unused resources usually excessive unused channels of neighbouring cells with densely populated cells to reduce handover failure rates. The neighboring cells share unused channels after fulfilling some conditional candidature criterion using threshold values so that they are not suffered themselves for starvation of channels in case of any abrupt change in traffic pattern. The cells are classified as ‘red’, ‘yellow’, or ‘green’, as per the available channels in cell which is governed by traffic pattern and thresholds. To combat the deficiency of channels in red cell, migration of unused channels from under-loaded cells, hierarchically from the qualified candidate neighboring cells is explored. The resources are returned back when the congested cell is capable of self-contained traffic management. In either of the cases conditional sharing of resources is executed for enhanced traffic management so that User Equipment (UE) is provided uninterrupted services with high Quality of Service (QoS). The fuzzy logic-based simulation results show that the proposed algorithm is efficiently in coincidence with improved successful handoffs.

Keywords: candidate cell, channel sharing, fuzzy logic, handover, small cells

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9516 Two Wheels Differential Type Odometry for Robot

Authors: Abhishek Jha, Manoj Kumar

Abstract:

This paper proposes a new type of two wheels differential type odometry to estimate the next position and orientation of mobile robots. The proposed odometry is composed for two independent wheels with respective encoders. The two wheels rotate independently, and the change is determined by the difference in the velocity of the two wheels. Angular velocities of the two wheels are measured by rotary encoders. A mathematical model is proposed for the mobile robots to precisely move towards the goal. Using measured values of the two encoders, the current displacement vector of a mobile robot is calculated by kinematics of the mathematical model. Using the displacement vector, the next position and orientation of the mobile robot are estimated by proposed odometry. Result of simulator experiment by the developed odometry is shown.

Keywords: mobile robot, odometry, unicycle, differential type, encoders, infrared range sensors, kinematic model

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9515 Evaluation of Trabectedin Safety and Effectiveness at a Tertiary Cancer Center at Qatar: A Retrospective Analysis

Authors: Nabil Omar, Farah Jibril, Oraib Amjad

Abstract:

Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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9514 From Pink to Ink: Understanding the Decision-Making Process of Post-mastectomy Women Who Have Covered Their Scars with Decorative Tattoos

Authors: Fernanda Rodriguez

Abstract:

Breast cancer is pervasive among women, and an increasing number of women are opting for a mastectomy: a medical operation in which one or both breasts are removed with the intention of treating or averting breast cancer. However, there is an emerging population of cancer survivors in European nations that, rather than attempting to reconstruct their breasts to resemble as much as possible ‘normal’ breasts, have turned to dress their scars with decorative tattoos. At a practical level, this study hopes to improve the support systems of these women by possibly providing professionals in the medical field, tattoo artists, and family members of cancer survivors with a deeper understanding of their motivations and decision-making processes for choosing an alternative restorative route - such as decorative tattoos - after their mastectomy. At an intellectual level, however, this study aims to narrow a gap in the academic field concerning the relationship between mastectomies and alternative methods of healing, such as decorative tattoos, as well as to broaden the understanding regarding meaning-making and the ‘normal’ feminine body. Thus, by means of semi-structured interviews and a phenomenological standpoint, this research set itself the goal to understand why do women who have undergone a mastectomy choose to dress their scars with decorative tattoos instead of attempting to regain ‘normalcy’ through breast reconstruction or 3D areola tattoos? The results obtained from the interviews with fifteen women showed that the disillusionment with one part of the other of breast restoration techniques had led these women to find an alternative form of healing that allows them not only to close a painful chapter of their life but also to regain control over their bodies after a period of time in which agency was taking away from them. Decorative post-mastectomy tattoos allow these women to grant their bodies with new meanings and produce their own interpretation of their feminine body and identity.

Keywords: alternative femininity, decorative mastectomy tattoos, gender embodiment, social stigmatization

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9513 Seamless Mobility in Heterogeneous Mobile Networks

Authors: Mohab Magdy Mostafa Mohamed

Abstract:

The objective of this paper is to introduce a vertical handover (VHO) algorithm between wireless LANs (WLANs) and LTE mobile networks. The proposed algorithm is based on the fuzzy control theory and takes into consideration power level, subscriber velocity, and target cell load instead of only power level in traditional algorithms. Simulation results show that network performance in terms of number of handovers and handover occurrence distance is improved.

Keywords: vertical handover, fuzzy control theory, power level, speed, target cell load

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9512 Challenges and Practical Tips for Advance Care Planning and End-of-Life Communications With Cancer Patients in Global Pandemic

Authors: Poonam Goswami

Abstract:

Background: The diagnosis of a serious illness like cancer can have an impact on a patient’s emotional well-being and may result in psychological symptoms, anxiety, depression, and loss of control. Advance care planning discussions ensure patients’ values and goals of care, including patients’ freedom to choose their place of death, are respected. Unfortunately, these discussions are often delayed and are not initiated early in patients’ cancer trajectory. As a result, patients’ wishes often remains unknown until the last phase of their life. Evidence suggests that many patients inappropriately receive aggressive treatment near the end of life, which does lead to higher resource utilization, decreased quality of life, and increased cost. Additionally, the novel coronavirus disease 2019 (COVID-19) pandemic challenged the health care systems worldwide and raised important ethical issues, especially regarding the potential need for rationing health care in the context of scarce resources and crisis capacity. The importance of goal concordant care is now even substantially important and is heightened in the context of this pandemic. Problem: Although there is growing evidence on the effects of the ACP on the completion of advanced directives, improved patient and family concordance for preferences for medical care, and receipt of care, there is still a lack of standardized ACP conversation strategies for patients with cancer. Methods: The Key concepts of ACP include (1) assessing patient and family readiness, (2) identifying a surrogate decision maker ( medical power of attorney), (3) exploring patient and family understanding of the disease and treatment options,(4) discussing the values and goals of care, and options for end-of-life care, (5) documenting patient preferences in the medical record, and (6) revisiting the discussions at every change in the treatment plan and /or change in clinical status, including at every hospitalization. Conclusion/Implication for practice: Advance Care Planning (ACP) and end-of-life (EOL) discussions are important for patients, families, and health care providers. Adopting the verbal and nonverbal communication strategies can help overcome the barriers to effective communication on these difficult discussions. ACP with goals of care discussions should not be delayed until the patient is hospitalized.

Keywords: advance care planning, end of life, cancer, global, pandemic

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9511 The Effectiveness of Warm-Water Footbath on Fatigue in Cancer Patient Undergoing Chemotherapy

Authors: Yu-Wen Lin, Li-Ni Liu

Abstract:

Introduction: Fatigue is the most common symptoms experienced by cancer patients undergoing chemotherapy. Patients receiving anticancer therapies develop a higher proportion of fatigue compared with patients who do not receive anticancer therapies. Fatigue has significant impacts on quality of life, daily activities, mood status, and social behaviors. A warm-water footbath (WWF) at 41℃ promotes circulation and removes metabolites resulting in improving sleep and relieving fatigue. The aim of this study is to determine the effectiveness of WWF for relieving fatigue with cancer patients undergoing chemotherapy. Materials and Methods: This is a single-center, prospective, quasi-experimental design study in the oncology ward in Taiwan. Participants in this study were assigned to WWF group as experimental group and standard care group as a control group by purposive sampling. In the WWF group, the participants were asked to soak their feet in 42-43℃ water 15 minutes for consecutive 6 days at one day before chemotherapy. Each participant was evaluated for fatigue level by the Taiwanese version of the Brief Fatigue Inventory (BFI-T). BFI-T was completed for consecutive 8 days of the study. The primary outcome was compared the BFI-T score of WWF group to the standard care group. Results: There were 60 participants enrolled in this study. Thirty participants were assigned to WWF group and 30 participants were assigned to standard care group. Both groups have comparable characteristic. The BFI-T scores of both groups were increased associated with the days of chemotherapy. The highest BFI-T scores of both groups were on the day 4 of chemotherapy. The BFI-T scores of both groups were decreased since day 5 and significantly decreased in WWF group on day 5 compared to standard care group (4.17 vs. 5.7, P < .05). At the end of the study the fatigue at its worse were significantly decreased in WWF group (2.33 vs. 4.37, P < .001). There was no adverse event reported in this study. Conclusion: WWF is an easy, safe, non-invasive, and relatively inexpensive nursing intervention for improving fatigue of cancer patients undergoing chemotherapy. In summary, this study shows the WWF is a simple complementary care method, and it is effective for improving and relieving fatigue in a short time. Through improving fatigue is a way to enhance the quality of life which is important for cancer patients undergoing chemotherapy. Larger prospective randomized controlled trial and long-term effectiveness and outcomes of WWF should be performed to confirm this study.

Keywords: chemotherapy, warm-water footbath, fatigue, Taiwanese version of the brief fatigue inventory

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9510 Value of FOXP3 Expression in Prediction of Neoadjuvant Chemotherapy Effect in Triple Negative Breast Cancer

Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

Abstract:

Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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9509 Development of a Humanized Anti-CEA Antibody for the Near Infrared Optical Imaging of Cancer

Authors: Paul J Yazaki, Michael Bouvet, John Shively

Abstract:

Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

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9508 Effect of Neem (Aziradicta Indica) Leaf Meal on Growth Performance, Haematology and Serum Biochemistry Indices of Broilers Not Administered Vaccines and Antibiotics

Authors: Ugwuowo Leonard Chidi, Oparaji Chetachukwu Jecinta., Ogidi Chibuzor Agafenachukwu, Onuoha Rebecca Obianuju

Abstract:

This experiment was conducted to investigate the growth performance, haematology and serum biochemistry indices of broiler birds fed diets containing Neem leaf meal. A total of 96 unsexed day-old broiler birds were allocated to four treatments of T1, T2, T3 and T4 and replicated three times with eight birds per replicate in a Completely Randomized Design. The treatments were diets containing 2.0, 4.0, 6.0 and 8.0% Neem leaf meal respectively. Growth performances, packed cell volume, red blood cell count, haemoglobin, white blood cell count, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count, aspartate amino transaminase, alanine amino transaminase, alkaline phosphate, cholesterol, albumin, globulin, urea, glucose, total protein and creatinine were evaluated. Results showed that there were no significant differences (P>0.05) in all the growth performance parameters among the treatments. The results of the experiment showed that there were significant differences (P<0.05) in all the heamatological and serum biochemistry parameters at finisher phases. Mean corpuscular volume, white blood cell count, lymphocytes, red blood cell count, haemoglobin, platelet count, creatinine and triglyceride increased and were highest in treatment two while treatment four had the least values in mean corpuscular volume, urea, white blood cell, haemoglobin and triglyceride. This implies that the levels of inclusion of Neem leaf meal in this experiment did not affect the growth performance of the broiler chicks but the haematological and serum biochemistry indices were affected. Treatment two with a 4% inclusion level of Neem leaf meal has shown the capacity to replace vaccines and antibiotics in broilers due to the positive effects it had on both the haematological and serum biochemistry.

Keywords: leaf meal, broiler, Aziradicta indica, serum biochemistry, haematology

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9507 Role of F18-FDG PET in Management of Differentiated Thyroid Cancers (TENIS) Patients

Authors: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

Abstract:

Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

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9506 A One Dimensional Particle in Cell Model for Excimer Lamps

Authors: W. Benstaali, A. Belasri

Abstract:

In this work we study a planar lamp filled with neon-xenon gas. We use a one-dimensional particle in a cell with Monte Carlo simulation (PIC-MCC) to investigate the effect xenon concentration on the energy deposited on excitation, ionization and ions. A Xe-Ne discharge is studied for a gas pressure of 400 torr. The results show an efficient Xe20-Ne mixture with an applied voltage of 1.2KV; the xenon excitation energy represents 65% form total energy dissipated in the discharge. We have also studied electrical properties and the energy balance a discharge for Xe50-Ne which needs a voltage of 2kv; the xenon energy is than more important.

Keywords: dielectric barrier discharge, efficiency, excitation, lamps

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9505 Microbial Fuel Cells in Waste Water Treatment and Electricity Generation

Authors: Rajalaxmi N., Padma Bhat, Pooja Garag, Pooja N. M., V. S. Hombalimath

Abstract:

Microbial fuel cell (MFC) is the advancement of science that aims at utilizing the oxidizing potential of bacteria for wastewater treatment and production of bio-hydrogen and bio-electricity. Salt-bridge is the economic alternative to highly priced proton-exchange membrane in the construction of a microbial fuel cell. This paper studies the electricity generating capacity of E.coli and Clostridium sporogenes in microbial fuel cells (MFCs). Unlike most of MFC research, this targets the long term goals of renewable energy production and wastewater treatment. In present study the feasibility and potential of bioelectricity production from different wastewater was observed. Different wastewater was primarily treated which were confirmed by the COD tests which showed reduction of COD. We observe that the electricity production of MFCs decreases almost linearly after 120 hrs. The sewage wastewater containing Clostridium sporogenes showed bioelectricity production up to 188mV with COD removal of 60.52%. Sewage wastewater efficiently produces bioelectricity and this also helpful to reduce wastewater pollution load.

Keywords: microbial fuel cell, bioelectricity, wastewater, salt bridge, COD

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9504 Effect of Copper Ions Doped-Hydroxyapatite 3D Fiber Scaffold

Authors: Adil Elrayah, Jie Weng, Esra Suliman

Abstract:

The mineral in human bone is not pure stoichiometric calcium phosphate (Ca/P) as it is partially substituted by in organic elements. In this study, the copper ions (Cu2+) substituted hydroxyapatite (CuHA) powder has been synthesized by the co-precipitation method. The CuHA powder has been used to fabricate CuHA fiber scaffolds by sol-gel process and the following sinter process. The resulted CuHA fibers have slightly different microstructure (i.e. porosity) compared to HA fiber scaffold, which is denser. The mechanical properties test was used to evaluate CuHA, and the results showed decreases in both compression strength and hardness tests. Moreover, the in vitro used endothelial cells to evaluate the angiogenesis of CuHA. The result illustrated that the viability of endothelial cell on CuHA fiber scaffold surfaces tends to antigenic behavior. The results obtained with CuHA scaffold give this material benefit in biological applications such as antimicrobial, antitumor, antigens, compacts, filling cavities of the tooth and for the deposition of metal implants anti-tumor, anti-cancer, bone filler, and scaffold.

Keywords: fiber scaffold, copper ions, hydroxyapatite, in vitro, mechanical property

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9503 Impact of Climate Change on Some Physiological Parameters of Cyclic Female Egyptian Buffalo

Authors: Nabil Abu-Heakal, Ismail Abo-Ghanema, Basma Hamed Merghani

Abstract:

The aim of this investigation is to study the effect of seasonal variations in Egypt on hematological parameters, reproductive and metabolic hormones of Egyptian buffalo-cows. This study lasted one year extending from December 2009 to November 2010 and was conducted on sixty buffalo-cows. Group of 5 buffalo-cows at estrus phase were selected monthly. Then, after blood sampling through tail vein puncture in the 2nd day after natural service, they were divided in two samples: one with anticoagulant for hematological analysis and the other without anticoagulant for serum separation. Results of this investigation revealed that the highest atmospheric temperature was in hot summer 32.61±1.12°C versus 26.18±1.67°C in spring and 19.92±0.70°C in winter season, while the highest relative humidity % was in winter season 43.50±1.60% versus 32.50±2.29% in summer season. The rise in temperature-humidity index from 63.73±1.29 in winter to 78.53±1.58 in summer indicates severe heat stress which is associated with significant reduction in total red blood cell count (3.20±0.15×106), hemoglobin concentration (8.83±0.43 g/dl), packed cell volume (30.73±0.12%), lymphocytes % (40.66±2.33 %), serum progesterone hormone concentration (0.56±0.03 ng/mll), estradiol17-B concentration (16.8±0.64 ng/ml), triiodothyronin (T3) concentration (2.33±0.33 ng/ml) and thyroxin hormone (T4) concentration (21.66±1.66 ng/ml), while hot summer resulted in significant increase in mean cell volume (96.55±2.25 fl), mean cell hemoglobin (30.81±1.33 pg), total white blood cell count (10.63±0.97×103), neutrophils % (49.66±2.33%), serum prolactin hormone (PRL) concentration (23.45±1.72 ng/ml) and cortisol hormone concentration (4.47±0.33 ng/ml) compared to winter season. There was no significant seasonal variation in mean cell hemoglobin concentration (MCHC). It was concluded that in Egypt there was a seasonal variation in atmospheric temperature, relative humidity, temperature humidity index (THI) and the rise in THI above the upper critical level (72 units), which, for lactating buffalo-cows in Egypt is the major constraint on buffalo-cows' hematological parameters and hormonal secretion that affects animal reproduction. Hence, we should improve climatic conditions inside the dairy farm to eliminate or reduce summer infertility.

Keywords: buffalo, climate change, Egypt, physiological parameters

Procedia PDF Downloads 660
9502 The Effect of Combined Fluid Shear Stress and Cyclic Stretch on Endothelial Cells

Authors: Daphne Meza, Louie Abejar, David A. Rubenstein, Wei Yin

Abstract:

Endothelial cell (ECs) morphology and function is highly impacted by the mechanical stresses these cells experience in vivo. Any change in the mechanical environment can trigger pathological EC responses. A detailed understanding of EC morphological response and function upon subjection to individual and simultaneous mechanical stimuli is needed for advancement in mechanobiology and preventive medicine. To investigate this, a programmable device capable of simultaneously applying physiological fluid shear stress (FSS) and cyclic strain (CS) has been developed, characterized and validated. Its validation was performed both experimentally, through tracer tracking, and theoretically, through the use of a computational fluid dynamics model. The effectiveness of the device was evaluated through EC morphology changes under mechanical loading conditions. Changes in cell morphology were evaluated through: cell and nucleus elongation, cell alignment and junctional actin production. The results demonstrated that the combined FSS-CS stimulation induced visible changes in EC morphology. Upon simultaneous fluid shear stress and biaxial tensile strain stimulation, cells were elongated and generally aligned with the flow direction, with stress fibers highlighted along the cell junctions. The concurrent stimulation from shear stress and biaxial cyclic stretch led to a significant increase in cell elongation compared to untreated cells. This, however, was significantly lower than that induced by shear stress alone, indicating that the biaxial tensile strain may counteract the elongating effect of shear stress to maintain the shape of ECs. A similar trend was seen in alignment, where the alignment induced by the concurrent application of shear stress and cyclic stretch fell in between that induced by shear stress and tensile stretch alone, indicating the opposite role shear stress and tensile strain may play in cell alignment. Junctional actin accumulation was increased upon shear stress alone or simultaneously with tensile stretch. Tensile stretch alone did not change junctional actin accumulation, indicating the dominant role of shear stress in damaging EC junctions. These results demonstrate that the shearing-stretching device is capable of applying well characterized dynamic shear stress and tensile strain to cultured ECs. Using this device, EC response to altered mechanical environment in vivo can be characterized in vitro.

Keywords: cyclic stretch, endothelial cells, fluid shear stress, vascular biology

Procedia PDF Downloads 377
9501 The Cell Viability Study of Extracts of Bark, Flowers, Leaves and Seeds of Indian Dhak Tree, Flame of Forest

Authors: Madhavi S. Apte, Milind Bhitre

Abstract:

In pharmaceutical research and new drug development, medicinal plants have important roles. Similarly, Indian dhak tree belonging to family Fabaceae has been widely used in the traditional Indian medical system of ‘Ayurveda’ for the treatment of a variety of ailments. Hence the cell viability study was undertaken to evaluate and compare the activity of extracts of various parts like flower, bark, leaf, seed by conducting MTT assay method along with other pharmacognostical studies. The methanolic extracts of bark, flowers, leaves, and seeds were used for the study. The cell viability MTT assay was performed using the standard operating procedures. The extracts were dissolved in DMSO and serially diluted with complete medium to get the concentrations range of test concentration. DMSO concentration was kept < 0.1% in all the samples. HUVEC cells maintained in appropriate conditions were seeded in 96 well plates and treated with different concentrations of the test samples and incubated at 37°C, 5% CO₂ for 96 hours. MTT reagent was added to the wells and incubated for 4 hours; the dark blue formazan product formed by the cells was dissolved in DMSO under a safety cabinet and read at 550nm. Percentage inhibitions were calculated and plotted with the concentrations used to calculate the IC50 values. The bark, flower, leaves and seed extracts have shown the cytotoxicity activity and can be further studied for antiangiogenesis activity.

Keywords: pharmacognosy, Cell viability, MTT assay, anti-angiogenesis

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9500 Data Analysis for Taxonomy Prediction and Annotation of 16S rRNA Gene Sequences from Metagenome Data

Authors: Suchithra V., Shreedhanya, Kavya Menon, Vidya Niranjan

Abstract:

Skin metagenomics has a wide range of applications with direct relevance to the health of the organism. It gives us insight to the diverse community of microorganisms (the microbiome) harbored on the skin. In the recent years, it has become increasingly apparent that the interaction between skin microbiome and the human body plays a prominent role in immune system development, cancer development, disease pathology, and many other biological implications. Next Generation Sequencing has led to faster and better understanding of environmental organisms and their mutual interactions. This project is studying the human skin microbiome of different individuals having varied skin conditions. Bacterial 16S rRNA data of skin microbiome is downloaded from SRA toolkit provided by NCBI to perform metagenomics analysis. Twelve samples are selected with two controls, and 3 different categories, i.e., sex (male/female), skin type (moist/intermittently moist/sebaceous) and occlusion (occluded/intermittently occluded/exposed). Quality of the data is increased using Cutadapt, and its analysis is done using FastQC. USearch, a tool used to analyze an NGS data, provides a suitable platform to obtain taxonomy classification and abundance of bacteria from the metagenome data. The statistical tool used for analyzing the USearch result is METAGENassist. The results revealed that the top three abundant organisms found were: Prevotella, Corynebacterium, and Anaerococcus. Prevotella is known to be an infectious bacterium found on wound, tooth cavity, etc. Corynebacterium and Anaerococcus are opportunist bacteria responsible for skin odor. This result infers that Prevotella thrives easily in sebaceous skin conditions. Therefore it is better to undergo intermittently occluded treatment such as applying ointments, creams, etc. to treat wound for sebaceous skin type. Exposing the wound should be avoided as it leads to an increase in Prevotella abundance. Moist skin type individuals can opt for occluded or intermittently occluded treatment as they have shown to decrease the abundance of bacteria during treatment.

Keywords: bacterial 16S rRNA , next generation sequencing, skin metagenomics, skin microbiome, taxonomy

Procedia PDF Downloads 172
9499 Self-Care and Risk Behaviors in Primary Caregiver of Cancer Patients

Authors: Ivonne N. Pérez-Sánchez. María L. Rascón- Gasca, Angélica Riveros-Rosas, Rebeca Robles García

Abstract:

Introduction: Primary caregivers of cancer patients have health problems related to their lack of time, stress, and fiscal strain. Their health problems could affect their patients’ health and also increase the expenses in public health. Aim: To describe self-care and risk behaviors in a sample of Mexican primary caregiver and the relation of these behaviors with emotional distress (caregiver burden, anxiety and depression symptoms), coping and sociodemographic variables. Method: Participated in this study 173 caregivers of a third level reference medical facility (age: M=49.4, SD=13.5) females 78%, males 22%, 57.5% were caregivers of patients with terminal cancer (CPTC), and 40.5% were caregivers of patients on oncology treatment (CPOT). Results: The 75.7% of caregivers reported to have had health problem in last six months as well as several symptoms which were related to emotional distress, these symptoms were more frequently between CPTC and female caregivers. A half (47.3%) of sample reported have had difficulties in caring their health; these difficulties were related to emotional distress and lower coping, more affected caregivers were who attend male patients and CPTC. The 76.8% of caregivers had health problems in last six months, but 26.5% of them waited to search medical care until they were very sick, and 11% didn't do it. Also, more than a half of sample (56.1%) admitted to have risk behaviors as drink alcohol, smoke or overeating for feeling well, these caregivers showed high emotional distress and lower coping. About caregivers healthy behaviors, 80% of them had a hobby; 27.2% do exercise usually and between 12% to 60% did medical checkups (glucose tests, blood pressure and cholesterol tests, eye exams and watched their weight), these caregivers had lower emotional distress and high coping, some variables related health behaviors were: care only one patient or a female patient and be a CPOT, social support, high educational level and experience as a caregiver in past. The half of caregivers were worrying to develop cancer in the future; this idea was 2.5 times more frequent in caregiver with problems to care their health. Conclusions: The results showed a big proportion of caregivers with medical problems. High emotional distress and low coping were related to physical symptoms, risk behaviors, and low self-care; poor self-care was frequently even in caregiver who have chronic illness.

Keywords: cancer, primary caregiver, risk behaviors, self-care

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9498 A Multi-Omic Assessment of Biomass and Pigment Accumulation in Nitrogen Deplete Conditions in Scenedesmus 46B-D3

Authors: Galen Dennis, Lukas Dahlin, Michael Guarnieri, Stefanie Van Wychen, Shawn Starkenburg, Matthew Posewitz, Colin Kruse

Abstract:

Scenedesmus 46B-D3 was identified in 2021 by screening a culture collection produced by the Posewitz lab at the Colorado School of Mines. The strain was found to continue accumulating biomass in a nitrogen-depleted state, which is a rare and technologically promising trait in microalgae. As the culture grows, a shift from nitrogen-replete to depleted conditions is indicated by arrested cell division and the accumulation of lipids, polysaccharides and photoprotective pigments. The latter trait gives stationary phase cultures a deep red color due to the presence of the high-value beta-ketocarotenoids, canthaxanthin and astaxanthin. The combination of continued photosynthesis post-nitrogen depletion and the accumulation of valuable pigments makes S. 46B-D3 of interest from a fundamental and industrial perspective, respectively. This project reports the results of a multi-omic study examining changes in the proteome and transcriptome in nitrogen-replete and deplete conditions. In addition, it characterizes the pigment composition of S. 46B-D3 across its growth curve and the method of cell division within the strain. These results indicate that upon sensing nitrogen scarcity, S. 46B-D3 efficiently recycles and repurposes nitrogen away from cell division and towards energy storage through the accumulation of lipids and polysaccharides. The accumulation of photoprotective pigments also prevents damage to and serves as an additional carbon sink for the cell’s light system.

Keywords: pigments, photosynthesis, proteomics, transcriptomics

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9497 High-Dimensional Single-Cell Imaging Maps Inflammatory Cell Types in Pulmonary Arterial Hypertension

Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

Abstract:

Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

Procedia PDF Downloads 174
9496 Different in Factors of the Distributor Selection for Food and Non-Food OTOP Entrepreneur in Thailand

Authors: Phutthiwat Waiyawuththanapoom

Abstract:

This study has only one objective which is to identify the different in factors of choosing the distributor for food and non-food OTOP entrepreneur in Thailand. In this research, the types of OTOP product will be divided into two groups which are food and non-food. The sample for the food type OTOP product was the processed fruit and vegetable from Nakorn Pathom province and the sample for the non-food type OTOP product was the court doll from Ang Thong province. The research was divided into 3 parts which were a study of the distribution pattern and how to choose the distributor of the food type OTOP product, a study of the distribution pattern and how to choose the distributor of the non-food type OTOP product and a comparison between 2 types of products to find the differentiation in the factor of choosing distributor. The data and information was collected by using the interview. The populations in the research were 5 producers of the processed fruit and vegetable from Nakorn Pathom province and 5 producers of the court doll from Ang Thong province. The significant factor in choosing the distributor of the food type OTOP product is the material handling efficiency and on-time delivery but for the non-food type OTOP product is focused on the channel of distribution and cost of the distributor.

Keywords: distributor, OTOP, food and non-food, selection

Procedia PDF Downloads 355
9495 Using Multi-Specialist Team to Care for a Breast Cancer Patient Who Received Total Mastectomy during Pregnancy

Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Heng-Hua Wang, Hui-Zhu Chen

Abstract:

This paper discusses the experience of caring for a patient diagnosed with breast cancer and later received total mastectomy during a 2nd trimester pregnancy. She was hospitalized from January 31 to February 4, 2018. Using 'Gordon’s 11 Functional Health Patterns' through physical exams and interviews, the researcher assessed the patient’s physical and mental health and determined the patient to have anxiety, acute pain, and body image disturbance. After establishing a strong relationship with the patient, the researcher helped the patient express her anxiety and personal feelings. A multi-specialist team was formed to evaluate both the patient and her unborn child, before, during, and after surgery. This individualized care allowed the patient and her child to optimize the post-operative results. Aside from medication, the patient also received non-medicinal treatment, including improvement of sleep quality with body positioning, diaphragmatic breathing exercises for pain and stress relief after surgery. Throughout hospitalization, the patient’s physical and emotional needs were addressed daily with listening sessions and empathy. The patient’s husband was also incorporated in the patient’s recovery by teaching both he and the patient how to change the sterile wound dressing, which may have the added benefit of improving marital relationships through shared activities of nurturing. The patient was also given advice about how to improve self-confidence through clothing. Lastly, the patient was encouraged to join a support group for breast cancer patients. Through the sharing of experience in groups and within the family, the patient was helped to adapt to the change of her appearance and re-establish her self-confidence. This level of care expedited the patient’s return to her family life and role of being a mother.

Keywords: anxiety, body image disturbance, breast cancer during pregnancy, multi-specialist team

Procedia PDF Downloads 98
9494 Establishing a Drug Discovery Platform to Progress Compounds into the Clinic

Authors: Sheraz Gul

Abstract:

The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

Procedia PDF Downloads 173
9493 Role of Long Noncoding RNA HULC on Colorectal Carcinoma Progression through Epigenetically Repressing NKD2 Expression

Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li

Abstract:

Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis

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9492 Characterization of a Dentigerous Cyst Cell Line and Its Secretion of Metalloproteinases

Authors: Muñiz-Lino Marcos A.

Abstract:

The ectomesenchymal tissues involved in tooth development and their remnants are the origin of different odontogenic lesions, including tumors and cysts of the jaws, with a wide range of clinical behaviors. A dentigerous cyst (DC) represents approximately 20% of all cases of odontogenic cysts, and it has been demonstrated that it can develop benign and malignant odontogenic tumors. DC is characterized by bone destruction of the area surrounding the crown of a tooth that has not erupted and contains liquid. The treatment of odontogenic tumors and cysts usually involves a partial or total removal of the jaw, causing important secondary co-morbidities. However, molecules implicated in DC pathogenesis, as well as in its development into odontogenic tumors, remain unknown. A cellular model may be useful to study these molecules, but that model has not been established yet. Here, we reported the establishment of a cell culture derived from a dentigerous cyst. This cell line was named DeCy-1. In spite of its ectomesenchymal morphology, DeCy-1 cells express epithelial markers such as cytokeratins 5, 6, and 8. Furthermore, these cells express the ODAM protein, which is present in odontogenesis and in dental follicles, indicating that DeCy-1 cells are derived from odontogenic epithelium. Analysis by electron microscopy of this cell line showed that it has a high vesicular activity, suggesting that DeCy-1 could secrete molecules that may be involved in DC pathogenesis. Thus, secreted proteins were analyzed by PAGE-SDS where we observed approximately 11 bands. In addition, the capacity of these secretions to degrade proteins was analyzed by gelatin substrate zymography. A degradation band of about 62 kDa was found in these assays. Western blot assays suggested that the matrix metalloproteinase 2 (MMP-2) is responsible for this protease activity. Thus, our results indicate that the establishment of a cell line derived from DC is a useful in vitro model to study the biology of this odontogenic lesion and its participation in the development of odontogenic tumors.

Keywords: dentigerous cyst, ameloblastoma, MMP-2, odontogenic tumors

Procedia PDF Downloads 40