Search results for: cancer specificity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2636

Search results for: cancer specificity

1796 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

Abstract:

Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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1795 Methodology for Diagnosing Architecture Improvements in a Cancer Hospital in Brasilia

Authors: Mariana Sabino, Janes Cleiton de Oliveira, Carlos Luna de Melo

Abstract:

This paper presents a discussion about the importance and influence of the environment in the patient’s recovery process. Some users (employees and patients) were submitted to a questionnaire that helps to diagnoses the major problems of the hospital, specially related to comfort (aesthetic, thermal, acoustic, light, ergonomic), well-being, how does the flow of patients and employees works in the hospital and wayfinding as well. After a short literature review presenting the topic, the hospital will be characterized, showing photos, the projects available and describing the hospital as well (how many rooms, functions of each one, receptions, waiting rooms, between other things.), than the questionnaire will be applied to patients and to the employees. Lastly the results of the answers given will be analyzed in graphics, and it will help to identify which are the major improvements needed immediately. This paper has the intention to propose a methodology to diagnose architecture problems in a cancer hospital in Brasilia, Brazil, besides to open a space to hear the people that use the building to tell about their discomforts and perceptions of the environment, it also will give an opportunity to apply the possible improvements. It is important to tell that it will be considered if the hospital has a healing environment, and it will also be considered the ergonomic issues about comfort and the way the system of this particular hospital works in general.

Keywords: cancer hospital, comfort, diagnose, healing environment

Procedia PDF Downloads 241
1794 Analysis of Relative Gene Expression Data of GATA3-AS1 Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients of Luminal B Subtype

Authors: X. Cervantes-López, C. Arriaga-Canon, L. Contreras Espinosa

Abstract:

The goal of this study is to validate the overexpression of the lncRNA GATA3-AS1 associated with resistance to neoadjuvant chemotherapy of female patients with locally advanced mammary adenocarcinoma of luminal B subtype This study involved a cohort of one hundred thirty-seven samples for which total RNA was isolated from formalin fixed paraffin embedded (FFPE) tissue. Samples were cut using a Microtome Hyrax M25 Zeiss and RNA was isolated using the RNeasy FFPE kit and a deparaffinization solution, the next step consisted in the analysis of RNA concentration and quality, then 18 µg of RNA was treated with DNase I, and cDNA was synthesized from 50 ng total RNA, finally real-time PCR was performed with SYBR Green/ROX qPCR Master Mix in order to determined relative gene expression using RPS28 as a housekeeping gene to normalize in a fold calculation ΔCt. As a result, we validated by real-time PCR that the overexpression of the lncRNA GATA3-AS1 is associated with resistance to neoadjuvant chemotherapy in locally advanced breast cancer patients of luminal B subtype.

Keywords: breast cancer, biomarkers, genomics, neoadjuvant chemotherapy, lncRNAS

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1793 Literature Review of Empirical Studies on the Psychological Processes of End-of-Life Cancer Patients

Authors: Kimiyo Shimomai, Mihoko Harada

Abstract:

This study is a literature review of the psychological reactions that occur in end-of-life cancer patients who are nearing death. It searched electronic databases and selected literature related to psychological studies of end-of-life patients. There was no limit on the search period, and the search was conducted until the second week of December 2021. The keywords were specified as “death and dying”, “terminal illness”, “end-of-life”, “palliative care”, “psycho-oncology” and “research”. These literatures referred to Holly (2017): Comprehensive Systematic Review for Advanced Practice Nursing, P268 Figure 10.3 to ensure quality. These literatures were selected with a dissertation score of 4 or 5. The review was conducted in two stages with reference to the procedure of George (2002). First, these references were searched for keywords in the database, and then relevant references were selected from the psychology and nursing studies of end-of-life patients. The number of literatures analyzed was 76 for overseas and 17 for domestic. As for the independent variables, "physical variable" was the most common in 36 literatures (66.7%), followed by "psychological variable" in 35 literatures (64.8%), "spiritual variable" in 21 literatures (38%), and "social variable" in 17 literatures. (31.5%), "Variables related to medical care / treatment" were 16 literatures (29.6%). To summarize the relationship between these independent variables and the dependent variable, when the dependent variable is "psychological variable", the independent variables are "psychological variable", "social variable", and "physical variable". Among the independent variables, the physical variables were the most common. The psychological responses that occur in end-stage cancer patients who are nearing death are mutually influenced by psychological, social, and physical variables. Therefore, it supported the "total pain" advocated by Cicely Saunders.

Keywords: cancer patient, end-of-life, literature review, psychological process

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1792 Mammographic Multi-View Cancer Identification Using Siamese Neural Networks

Authors: Alisher Ibragimov, Sofya Senotrusova, Aleksandra Beliaeva, Egor Ushakov, Yuri Markin

Abstract:

Mammography plays a critical role in screening for breast cancer in women, and artificial intelligence has enabled the automatic detection of diseases in medical images. Many of the current techniques used for mammogram analysis focus on a single view (mediolateral or craniocaudal view), while in clinical practice, radiologists consider multiple views of mammograms from both breasts to make a correct decision. Consequently, computer-aided diagnosis (CAD) systems could benefit from incorporating information gathered from multiple views. In this study, the introduce a method based on a Siamese neural network (SNN) model that simultaneously analyzes mammographic images from tri-view: bilateral and ipsilateral. In this way, when a decision is made on a single image of one breast, attention is also paid to two other images – a view of the same breast in a different projection and an image of the other breast as well. Consequently, the algorithm closely mimics the radiologist's practice of paying attention to the entire examination of a patient rather than to a single image. Additionally, to the best of our knowledge, this research represents the first experiments conducted using the recently released Vietnamese dataset of digital mammography (VinDr-Mammo). On an independent test set of images from this dataset, the best model achieved an AUC of 0.87 per image. Therefore, this suggests that there is a valuable automated second opinion in the interpretation of mammograms and breast cancer diagnosis, which in the future may help to alleviate the burden on radiologists and serve as an additional layer of verification.

Keywords: breast cancer, computer-aided diagnosis, deep learning, multi-view mammogram, siamese neural network

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1791 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital

Authors: Rizwan Iqbal

Abstract:

Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

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1790 18 F-FDG PET/CT: Utility in Breast Cancer Surgery

Authors: R. Sonda, F. Pellini, A. Invento, S. Mirandola, F. Riolfatti, D. Grigolato, G. P. Pollini

Abstract:

The purpose of study is to assess utility of 18F-FDG PET/CT in patients with breast heteroplasia and possibility of changing the surgery/therapeutic treatment. Among these "under fourty-five" candidated for NAC, the prevalence of change in therapeutic approach in comparison with first and second level exams has been: 43.75%, while by 22% among the "over forty-five". The surgical timing according to first-level exams have been deferred in 31.46% cases; PET/CT has led to a change in therapeutic treatment of 48.31% on the previous given; then the addition of MRI has led to a similar variation. For all the total patients, the prevalent choice was found to the debulking approach by increasing from a prevalence of 12.92% to 15.17%, resulting in a reduction of conservative one.The present study set itself the objective to demonstrate how the FDG PET/CT could improve on breast imaging according to a more appropriate surgery.

Keywords: breast cancer, FGD PET/CT, preoperative staging, surgical approach

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1789 Modulation of Tamoxifen-Induced Cytotoxicity in Breast Cancer Cell Lines by 3-Bromopyruvate

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

Abstract:

Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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1788 Caspase-11 and AIM2 Inflammasome are Involved in Smoking-Induced COPD and Lung Adenocarcinoma

Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

Abstract:

Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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1787 Sparse Modelling of Cancer Patients’ Survival Based on Genomic Copy Number Alterations

Authors: Khaled M. Alqahtani

Abstract:

Copy number alterations (CNA) are variations in the structure of the genome, where certain regions deviate from the typical two chromosomal copies. These alterations are pivotal in understanding tumor progression and are indicative of patients' survival outcomes. However, effectively modeling patients' survival based on their genomic CNA profiles while identifying relevant genomic regions remains a statistical challenge. Various methods, such as the Cox proportional hazard (PH) model with ridge, lasso, or elastic net penalties, have been proposed but often overlook the inherent dependencies between genomic regions, leading to results that are hard to interpret. In this study, we enhance the elastic net penalty by incorporating an additional penalty that accounts for these dependencies. This approach yields smooth parameter estimates and facilitates variable selection, resulting in a sparse solution. Our findings demonstrate that this method outperforms other models in predicting survival outcomes, as evidenced by our simulation study. Moreover, it allows for a more meaningful interpretation of genomic regions associated with patients' survival. We demonstrate the efficacy of our approach using both real data from a lung cancer cohort and simulated datasets.

Keywords: copy number alterations, cox proportional hazard, lung cancer, regression, sparse solution

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1786 Autophagy Suppresses Tumorigenesis through Upregulation of MiR-449a in Colorectal Cancer

Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

Abstract:

Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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1785 Anti-proliferative Activity and HER2 Receptor Expression Analysis of MCF-7 (Breast Cancer Cell) Cells by Plant Extract Coleus Barbatus (Andrew)

Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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1784 Synthesis of Porphyrin-Functionalized Beads for Flow Cytometry

Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

Abstract:

Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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1783 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell

Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity

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1782 Going Horizontal: Confronting the Challenges When Transitioning to Cloud

Authors: Harvey Hyman, Thomas Hull

Abstract:

As one of the largest cancer treatment centers in the United States, we continuously confront the challenge of how to leverage the best possible technological solutions, in order to provide the highest quality of service to our customers – the doctors, nurses and patients at Moffitt who are fighting every day for the prevention and cure of cancer. This paper reports on the transition from a vertical to a horizontal IT infrastructure. We discuss how the new frameworks and methods such as public, private and hybrid cloud, brokering cloud services are replacing the traditional vertical paradigm for computing. We also report on the impact of containers, micro services, and the shift to continuous integration/continuous delivery. These impacts and changes in delivery methodology for computing are driving how we accomplish our strategic IT goals across the enterprise.

Keywords: cloud computing, IT infrastructure, IT architecture, healthcare

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1781 Isolation of Cytotoxic Compound from Tectona grandis Stem to Be Used as Thai Medicinal Preparation for Cancer Treatment

Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat

Abstract:

A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.

Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone

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1780 Improving the Accuracy of Oral Care Performed by ICU Nurses for Cancer Patients

Authors: Huang Wei-Yi

Abstract:

Purpose: Oral cancer patients undergoing skin flap reconstruction may have wounds in the oral cavity, leading to accumulation of blood, clots, and secretions. Inadequate oral care by nursing staff can result in oral infections and pain. Methods: An investigation revealed that ICU nurses' knowledge and adherence to oral care standards were below acceptable levels. Key issues identified included lack of hands-on training opportunities, insufficient experience, absence of oral care standards and regular audits, no in-service education programs, and a lack of oral care educational materials. Interventions: The following measures were implemented: 1) in-service education programs, 2) development of care standards, 3) creation of a monitoring plan, 4) bedside demonstration teaching, and 5) revision of educational materials. Results: The intervention demonstrated that ICU nurses' knowledge and adherence to oral care standards improved, leading to better quality oral care and reduced pain for patients. Conclusion: Through in-service education, bedside demonstrations, establishment of oral care standards, and regular audits, the oral care skills of ICU nurses were significantly enhanced, resulting in improved oral care quality and decreased patient pain.

Keywords: oral care, ICU, improving, oral cancer

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1779 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

Abstract:

Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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1778 Differentially Expressed Protein Biomarkers in Early and Advanced Stage Young Triple-Negative Breast Cancer Patients

Authors: Shamim Mushtaq, Moazzam Shahid

Abstract:

Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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1777 Anticancer Effect of Resveratrol-Loaded Gelatin Nanoparticles in NCI-H460 Non-Small Cell Lung Carcinoma Cell Lines

Authors: N. Rajendra Prasad

Abstract:

Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

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1776 Profiling of the Cell-Cycle Related Genes in Response to Efavirenz, a Non-Nucleoside Reverse Transcriptase Inhibitor in Human Lung Cancer

Authors: Rahaba Marima, Clement Penny

Abstract:

The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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1775 Post-Traumatic Stress Disorder: Management at the Montfort Hospital

Authors: Kay-Anne Haykal, Issack Biyong

Abstract:

The post-traumatic stress disorder (PTSD) rises from exposure to a traumatic event and appears by a persistent experience of this event. Several psychiatric co-morbidities are associated with PTSD and include mood disorders, anxiety disorders, and substance abuse. The main objective was to compare the criteria for PTSD according to the literature to those used to diagnose a patient in a francophone hospital and to check the correspondence of these two criteria. 700 medical charts of admitted patients on the medicine or psychiatric unit at the Montfort Hospital were identified with the following diagnoses: major depressive disorder, bipolar disorder, anxiety disorder, substance abuse, and PTSD for the period of time between April 2005 and March 2006. Multiple demographic criteria were assembled. Also, for every chart analyzed, the PTSD criteria, according to the Manual of Mental Disorders (DSM) IV were found, identified, and grouped according to pre-established codes. An analysis using the receiver operating characteristic (ROC) method was elaborated for the study of data. A sample of 57 women and 50 men was studied. Age was varying between 18 and 88 years with a median age of 48. According to the PTSD criteria in the DSM IV, 12 patients should have the diagnosis of PTSD in opposition to only two identified in the medical charts. The ROC method establishes that with the combination of data from PTSD and depression, the sensitivity varies between 0,127 and 0,282, and the specificity varies between 0,889 and 0,917. Otherwise, if we examine the PTSD data alone, the sensibility jumps to 0.50, and the specificity varies between 0,781 and 0,895. This study confirms the presence of an underdiagnosed and treated PTSD that causes severe perturbations for the affected individual.

Keywords: post-traumatic stress disorder, co-morbidities, diagnosis, mental health disorders

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1774 Modified Acetamidobenzoxazolone Based Biomarker for Translocator Protein Mapping during Neuroinflammation

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

Abstract:

The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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1773 Study of Circulatory MiR-122 and MiR-130a Expression among Chronic Hepatitis C Egyptian Patients

Authors: Hend K. Moosa, Eman A. Rashwan, Ezzat M. Hassan, Amany A. Ghazy, Amel G. Sheredy

Abstract:

The stability of microRNA (miR) in the circulation can show a great progress toward the discovery of non-invasive diagnostic and prognostic biomarkers in many diseases. In the present study, circulatory miR-122 and miR-130a were analysed in chronic hepatitis C Egyptian patients in predicting the clinical outcome of interferon treatment. In addition, their expression levels were correlated to viral RNA levels, necro-inflammatory markers (AST, ALT) and to each other. This study was conducted on 51 subjects where 36 were chronic HCV patients in which they were divided into naive and interferon treated HCV patients (responders and non-responders) and 15 matched healthy controls. Serum quantification of miR-122 and miR-130a were performed by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The results showed a significant upregulation of miR-122 in non-responder patients (P=0.049). By receiver operating characteristic analysis curve, miR-122 revealed 65% sensitivity and 92.3% specificity in predicting non-responsiveness of patients to IFN treatment, while miR-130a showed a sensitivity of 100% and specificity of 53.85%. Remarkably, there was a significant positive correlation between miR-122 and miR-130a in naive HCV patients (r=0.714, p=0.003). However, there was no significant correlation between serum miR-122, miR-130a expression levels and necro-inflammatory markers (AST, ALT). To conclude, miR-122 and miR-130a have a significant association with viral RNA levels and accordingly, they may have a synergistic power in promoting viral replication. Interestingly, miR-122 and miR-130a have a predictive power in predicting clinical outcome of IFN treatment which can be further studied in currently used drugs in order to reduce the socio-economic burden of potentially non-responders.

Keywords: hepatitis C, microRNA, miR-122, miR-130a

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1772 SIRT1 Gene Polymorphisms and Its Protein Level in Colorectal Cancer

Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

Abstract:

Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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1771 Understanding Jordanian Women's Values and Beliefs Related to Prevention and Early Detection of Breast Cancer

Authors: Khlood F. Salman, Richard Zoucha, Hani Nawafleh

Abstract:

Introduction: Jordan ranks the fourth highest breast cancer prevalence after Lebanon, Bahrain, and Kuwait. Considerable evidence showed that cultural, ethnic, and economic differences influence a woman’s practice to early detection and prevention of breast cancer. Objectives: To understand women’s health beliefs and values in relation to early detection of breast cancer; and to explore the impact of these beliefs on their decisions regarding reluctance or acceptance of early detection measures such as mammogram screening. Design: A qualitative focused ethnography was used to collect data for this study. Settings: The study was conducted in the second largest city surrounded by a large rural area in Ma’an- Jordan. Participants: A total of twenty seven women, with no history of breast cancer, between the ages of 18 and older, who had prior health experience with health providers, and were willing to share elements of personal health beliefs related to breast health within the larger cultural context. The participants were recruited using the snowball method and words of mouth. Data collection and analysis: A short questionnaire was designed to collect data related to socio demographic status (SDQ) from all participants. A Semi-structured interviews guide was used to elicit data through interviews with the informants. Nvivo10 a data manager was utilized to assist with data analysis. Leininger’s four phases of qualitative data analysis was used as a guide for the data analysis. The phases used to analyze the data included: 1) Collecting and documenting raw data, 2) Identifying of descriptors and categories according to the domains of inquiry and research questions. Emic and etic data is coded for similarities and differences, 3) Identifying patterns and contextual analysis, discover saturation of ideas and recurrent patterns, and 4) Identifying themes and theoretical formulations and recommendations. Findings: Three major themes were emerged within the cultural and religious context; 1. Fear, denial, embarrassment and lack of knowledge were common perceptions of Ma’anis’ women regarding breast health and screening mammography, 2. Health care professionals in Jordan were not quick to offer information and education about breast cancer and screening, and 3. Willingness to learn about breast health and cancer prevention. Conclusion: The study indicated the disparities between the infrastructure and resourcing in rural and urban areas of Jordan, knowledge deficit related to breast cancer, and lack of education about breast health may impact women’s decision to go for a mammogram screening. Cultural beliefs, fear, embarrassments as well as providers lack of focus on breast health were significant contributors against practicing breast health. Health providers and policy makers should provide resources for the establishment health education programs regarding breast cancer early detection and mammography screening. Nurses should play a major role in delivering health education about breast health in general and breast cancer in particular. A culturally appropriate health awareness messages can be used in creating educational programs which can be employed at the national levels.

Keywords: breast health, beliefs, cultural context, ethnography, mammogram screening

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1770 International Classification of Primary Care as a Reference for Coding the Demand for Care in Primary Health Care

Authors: Souhir Chelly, Chahida Harizi, Aicha Hechaichi, Sihem Aissaoui, Leila Ben Ayed, Maha Bergaoui, Mohamed Kouni Chahed

Abstract:

Introduction: The International Classification of Primary Care (ICPC) is part of the morbidity classification system. It had 17 chapters, and each is coded by an alphanumeric code: the letter corresponds to the chapter, the number to a paragraph in the chapter. The objective of this study is to show the utility of this classification in the coding of the reasons for demand for care in Primary health care (PHC), its advantages and limits. Methods: This is a cross-sectional descriptive study conducted in 4 PHC in Ariana district. Data on the demand for care during 2 days in the same week were collected. The coding of the information was done according to the CISP. The data was entered and analyzed by the EPI Info 7 software. Results: A total of 523 demands for care were investigated. The patients who came for the consultation are predominantly female (62.72%). Most of the consultants are young with an average age of 35 ± 26 years. In the ICPC, there are 7 rubrics: 'infections' is the most common reason with 49.9%, 'other diagnoses' with 40.2%, 'symptoms and complaints' with 5.5%, 'trauma' with 2.1%, 'procedures' with 2.1% and 'neoplasm' with 0.3%. The main advantage of the ICPC is the fact of being a standardized tool. It is very suitable for classification of the reasons for demand for care in PHC according to their specificity, capacity to be used in a computerized medical file of the PHC. Its current limitations are related to the difficulty of classification of some reasons for demand for care. Conclusion: The ICPC has been developed to provide healthcare with a coding reference that takes into account their specificity. The CIM is in its 10th revision; it would gain from revision to revision to be more efficient to be generalized and used by the teams of PHC.

Keywords: international classification of primary care, medical file, primary health care, Tunisia

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1769 Expression of miRNA 335 in Gall Bladder Cancer: A Correlative Study

Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar

Abstract:

Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.

Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay

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1768 Evaluation of Cytotoxic Effect of Two Diterpenes from Plectranthus barbatus

Authors: Nawal Al Musayeib, Musarat Amina, Perwez Alam

Abstract:

Plectranthus barbatus Andrews (Lamiaceae) is the most common species of genus Plectranthus. It is used for treating various ailments. In this study, two rare diterpenes 11,14-dihydroxy-8,11,13-abietatrien-7-one (1) and 12-hydroxyabieta-8(14),9(11),12-trien-7-one (2) were isolated for the first time from P. barbatus. Their chemical structures were verified utilizing various spectroscopic experiments. The effect of diterpenes against undifferentiated/anaplastic thyroid cancer cell line (FRO) was evaluated and they were quantitatively analysed using HPTLC method. The two diterpenes were found to be cytotoxic, however compound 1 showed significant cytotoxic effects where 95% reduction in the cell viability was observed in different time intervals. The quantity of compound 1 and compound 2 in PBCE were found to be 2.04 and15.97 μg/mg, respectively of dried weight of the extract.

Keywords: abietatrien, cancer, diterpenes, Plectranthus barbatus

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1767 Exposure Assessment for Worker Exposed to Heavy Metals during Road Marking Operations

Authors: Yin-Hsuan Wu, Perng-Jy Tsai, Ying-Fang Wang, Shun-Hui Chung

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The present study was conducted to characterize exposure concentrations, concentrations deposited on the different respiratory regions, and resultant health risks associated with heavy metal exposures for road marking workers. Road marking workers of three similar exposure groups (SEGs) were selected, including the paint pouring worker, marking worker, and preparing worker. Personal exposure samples were collected using an inhalable dust sampler (IOM), and the involved particle size distribution samples were estimated using an eight-stage Marple personal cascade impactor during five working days. In total, 25 IOM samples and 20 Marple samples were collected. All collected samples were analyzed for their heavy metal contents using the ICP/MS. The resultant heavy metal particle size distributions were also used to estimate the fractions of particle deposited on the head airways (Chead), tracheobronchial (Cthorac) and alveolar regions (Cresp) of the exposed workers. In addition, Pb and Cr were selected to estimate the incremental cancer risk, and Zn, Ti, and Mo were selected to estimate the corresponding non-cancer risk in the present study. Results show that three heavy metals, including Pb, Cr, and Ti, were found with the highest concentrations for the SEG of the paint pouring worker (=0.585±2.98, 0.307±1.71, 0.902±2.99 μg/m³, respectively). For the fraction of heavy metal particle deposited on the respiratory tract, both alveolar and head regions were found with the highest values (=23-43% and 39-61%, respectively). For both SEGs of the paint pouring and marking, 51% of Cr, 59-61% of Zn, and 48-51% of Ti were found to be deposited on the alveolar region, and 41-43% of Pb was deposited on the head region. Finally, the incremental cancer risk for the SEGs of the paint pouring, marking, and preparing were found as 1.08×10⁻⁵, 2.78×10⁻⁶, and 2.20×10⁻⁶, respectively. In addition, the estimated non-cancer risk for the above three SEGs was found to be consistently less than unity. In conclusion, though the estimated non-cancer risk was less than unity, all resultant incremental cancer risk was greater than 10⁻⁶ indicating the abatement of workers’ exposure is necessary. It is suggested that strategies, including placing on the molten kettle, substitution the currently used paints for less heavy metal containing paints, and wearing fume protecting personal protective equipment can be considered in the future from reducing the worker’s exposure aspect.

Keywords: health risk assessment, heavy metal, respiratory track deposition, road marking

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