Search results for: cancer prediction
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4230

Search results for: cancer prediction

3300 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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3299 Formulation and Anticancer Evaluation of Beta-Sitosterol in Henna Methanolic Extract Embedded in Controlled Release Nanocomposite

Authors: Sanjukta Badhai, Durga Barik, Bairagi C. Mallick

Abstract:

In the present study, Beta-Sitosterol in Lawsonia methanolic leaf extract embedded in controlled release nanocomposite was prepared and evaluated for in vivo anticancer efficacy in dimethyl hydrazine (DMH) induced colon cancer. In the present study, colon cancer was induced by s.c injection of DMH (20 mg/kg b.wt) for 15 weeks. The animals were divided into five groups as follows control, DMH alone, DMH and Beta Sitosterol nanocomposite (50mg/kg), DMH and Beta Sitosterol nanocomposite (100 mg/kg) and DMH and Standard Silymarin (100mg/kg) and the treatment was carried out for 15 weeks. At the end of the study period, the blood was withdrawn, and serum was separated for haematological, biochemical analysis and tumor markers. Further, the colonic tissue was removed for the estimation of antioxidants and histopathological analysis. The results of the study displays that DMH intoxication elicits altered haematological parameters (RBC,WBC, and Hb), elevated lipid peroxidation and decreased antioxidants level (SOD, CAT, GPX, GST and GSH), elevated lipid profiles (cholesterol and triglycerides), tumor markers (CEA and AFP) and altered colonic tissue histology. Meanwhile, treatment with Beta Sitosterol nanocomposites significantly restored the altered biochemicals parameters in DMH induced colon cancer mediated by its anticancer efficacy. Further, Beta Sitosterol nanocomposite (100 mg/kg) showed marked efficacy.

Keywords: nanocomposites, herbal formulation, henna, beta sitosterol, colon cancer, dimethyl hydrazine, antioxidant, lipid peroxidation

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3298 Neo-Adjuvant B-CAT Chemotherapy in Triple Negative Breast Cancer

Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

Abstract:

Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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3297 A Lung Cancer Patients with Septic Shock Nursing Experience

Authors: Syue-Wen Lin

Abstract:

Objective: This article explores the nursing experience of an 84-year-old male lung cancer patient who underwent a thoracoscopic right lower lobectomy and treatment. The patient has multiple medical histories, including hypertension and diabetes. The nursing process involved cancer treatment, postoperative pain management, as well as wound care and healing. Methods: The nursing period is from February 10 to February 17, 2024. During the nursing process, pain management strategies are implemented, including morphine drugs and non-drug methods, and music therapy, essential oil massage, and extended reception time are used to make patients feel physically and mentally comfortable so as to reduce postoperative pain and encourage active participation in rehabilitation. Strict sterile wound dressing procedures and advanced wound care techniques are used to promote wound healing and prevent infection. Due to septic shock, dialysis is used to relieve worsening symptoms. Taking into account the patient's cancer status, the nursing team provides comprehensive cancer care based on the patient's physical and psychological needs. Given the complexity of the patient's condition, including advanced cancer, palliative care is also incorporated throughout the care process to relieve discomfort and provide psychological support. Results: Through comprehensive health assessment, the nursing team fully understood the patient's condition and developed a personalized care plan based on the patient's condition. The interprofessional critical care team provides respiratory therapy and lung expansion exercises to reduce muscle loss while addressing the patient's psychological status, pain management, and vital sign stabilization needs, resulting in a comprehensive approach to care. Lung expansion exercises and the use of a high-frequency chest wall oscillation vest successfully improved sputum drainage and facilitated weaning from mechanical ventilation. In addition, helping patients stabilize their vital signs and the integration of cancer care, pain management, wound care and palliative care helps the patient be fully supported throughout the recovery process, ultimately improving his quality of life. Conclusion: Lung cancer and septic shock present significant challenges to patients, and the nursing team not only provides critical care but also addresses the unique needs of patients through comprehensive infection control, cancer care, pain management, wound care, and palliative care interventions. These measures effectively improve patients' quality of life, promote recovery, and provide compassionate palliative care for terminally ill patients. Nursing staff work closely with family members to develop a comprehensive care plan to ensure that patients receive high-quality medical care as well as psychological support and a comfortable recovery environment.

Keywords: septic shock, lung cancer, palliative care, nursing experience

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3296 Drug-Based Nanoparticles: Comparative Study of the Effect Drug Type on Release Kinetics and Cell Viability

Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

Abstract:

The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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3295 Spatial Variability of Soil Metal Contamination to Detect Cancer Risk Zones in Coimbatore Region of India

Authors: Aarthi Mariappan, Janani Selvaraj, P. B. Harathi, M. Prashanthi Devi

Abstract:

Anthropogenic modification of the urban environment has largely increased in the recent years in order to sustain the growing human population. Intense industrial activity, permanent and high traffic on the roads, a developed subterranean infrastructure network, land use patterns are just some specific characteristics. Every day, the urban environment is polluted by more or less toxic emissions, organic or metals wastes discharged from specific activities such as industrial, commercial, municipal. When these eventually deposit into the soil, the physical and chemical properties of the surrounding soil is changed, transforming it into a human exposure indicator. Metals are non-degradable and occur cumulative in soil due to regular deposits are a result of permanent human activity. Due to this, metals are a contaminant factor for soil when persistent over a long period of time and a possible danger for inhabitant’s health on prolonged exposure. Metals accumulated in contaminated soil may be transferred to humans directly, by inhaling the dust raised from top soil, or by ingesting, or by dermal contact and indirectly, through plants and animals grown on contaminated soil and used for food. Some metals, like Cu, Mn, Zn, are beneficial for human’s health and represent a danger only if their concentration is above permissible levels, but other metals, like Pb, As, Cd, Hg, are toxic even at trace level causing gastrointestinal and lung cancers. In urban areas, metals can be emitted from a wide variety of sources like industrial, residential, commercial activities. Our study interrogates the spatial distribution of heavy metals in soil in relation to their permissible levels and their association with the health risk to the urban population in Coimbatore, India. Coimbatore region is a high cancer risk zone and case records of gastro intestinal and respiratory cancer patients were collected from hospitals and geocoded in ArcGIS10.1. The data of patients pertaining to the urban limits were retained and checked for their diseases history based on their diagnosis and treatment. A disease map of cancer was prepared to show the disease distribution. It has been observed that in our study area Cr, Pb, As, Fe and Mg exceeded their permissible levels in the soil. Using spatial overlay analysis a relationship between environmental exposure to these potentially toxic elements in soil and cancer distribution in Coimbatore district was established to show areas of cancer risk. Through this, our study throws light on the impact of prolonged exposure to soil contamination in soil in the urban zones, thereby exploring the possibility to detect cancer risk zones and to create awareness among the exposed groups on cancer risk.

Keywords: soil contamination, cancer risk, spatial analysis, India

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3294 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer

Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

Abstract:

Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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3293 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

Abstract:

Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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3292 Spatio-Temporal Risk Analysis of Cancer to Assessed Environmental Exposures in Coimbatore, India

Authors: Janani Selvaraj, M. Prashanthi Devi, P. B. Harathi

Abstract:

Epidemiologic studies conducted over several decades have provided evidence to suggest that long-term exposure to elevated ambient levels of particulate air pollution is associated with increased mortality. Air quality risk management is significant in developing countries and it highlights the need to understand the role of ecologic covariates in the association between air pollution and mortality. Several new methods show promise in exploring the geographical distribution of disease and the identification of high risk areas using epidemiological maps. However, the addition of the temporal attribute would further give us an in depth idea of the disease burden with respect to forecasting measures. In recent years, new methods developed in the reanalysis were useful for exploring the spatial structure of the data and the impact of spatial autocorrelation on estimates of risk associated with exposure to air pollution. Based on this, our present study aims to explore the spatial and temporal distribution of the lung cancer cases in the Coimbatore district of Tamil Nadu in relation to air pollution risk areas. A spatio temporal moving average method was computed using the CrimeStat software and visualized in ArcGIS 10.1 to document the spatio temporal movement of the disease in the study region. The random walk analysis performed showed the progress of the peak cancer incidences in the intersection regions of the Coimbatore North and South taluks that include major commercial and residential regions like Gandhipuram, Peelamedu, Ganapathy, etc. Our study shows evidence that daily exposure to high air pollutant concentration zones may lead to the risk of lung cancer. The observations from the present study will be useful in delineating high risk zones of environmental exposure that contribute to the increase of cancer among daily commuters. Through our study we suggest that spatially resolved exposure models in relevant time frames will produce higher risks zones rather than solely on statistical theory about the impact of measurement error and the empirical findings.

Keywords: air pollution, cancer, spatio-temporal analysis, India

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3291 Artificial Neural Network Based Parameter Prediction of Miniaturized Solid Rocket Motor

Authors: Hao Yan, Xiaobing Zhang

Abstract:

The working mechanism of miniaturized solid rocket motors (SRMs) is not yet fully understood. It is imperative to explore its unique features. However, there are many disadvantages to using common multi-objective evolutionary algorithms (MOEAs) in predicting the parameters of the miniaturized SRM during its conceptual design phase. Initially, the design variables and objectives are constrained in a lumped parameter model (LPM) of this SRM, which leads to local optima in MOEAs. In addition, MOEAs require a large number of calculations due to their population strategy. Although the calculation time for simulating an LPM just once is usually less than that of a CFD simulation, the number of function evaluations (NFEs) is usually large in MOEAs, which makes the total time cost unacceptably long. Moreover, the accuracy of the LPM is relatively low compared to that of a CFD model due to its assumptions. CFD simulations or experiments are required for comparison and verification of the optimal results obtained by MOEAs with an LPM. The conceptual design phase based on MOEAs is a lengthy process, and its results are not precise enough due to the above shortcomings. An artificial neural network (ANN) based parameter prediction is proposed as a way to reduce time costs and improve prediction accuracy. In this method, an ANN is used to build a surrogate model that is trained with a 3D numerical simulation. In design, the original LPM is replaced by a surrogate model. Each case uses the same MOEAs, in which the calculation time of the two models is compared, and their optimization results are compared with 3D simulation results. Using the surrogate model for the parameter prediction process of the miniaturized SRMs results in a significant increase in computational efficiency and an improvement in prediction accuracy. Thus, the ANN-based surrogate model does provide faster and more accurate parameter prediction for an initial design scheme. Moreover, even when the MOEAs converge to local optima, the time cost of the ANN-based surrogate model is much lower than that of the simplified physical model LPM. This means that designers can save a lot of time during code debugging and parameter tuning in a complex design process. Designers can reduce repeated calculation costs and obtain accurate optimal solutions by combining an ANN-based surrogate model with MOEAs.

Keywords: artificial neural network, solid rocket motor, multi-objective evolutionary algorithm, surrogate model

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3290 Sider Bee Honey: Antitumor Effect in Some Experimental Tumor Cell Lines

Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

Abstract:

Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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3289 Inhibitory Effect of P2Y1R Agonist 1-Indolinoalkyl 2-Phenolic Derivative on Prostate Cancer Cell Proliferation via the MAPK Signalling

Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Abstract:

Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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3288 Muslim Husbands’ Participation in Women’s Health and Illness: A Descriptive Exploratory Study Applied to Muslim Women in Indonesia

Authors: Restuning Widiasih, Katherine Nelson, Joan Skinner

Abstract:

Muslim husbands have significant roles in the family including their roles in women’s health and illness. However, studies that explore Muslim husbands’ participation in women’s health is limited. The objective of this study was to uncover Muslim husbands’ participation in women’ health and illness including cancer prevention and screening. A descriptive exploratory approach was used involving 20 Muslim women from urban and rural areas of West Java Province, Indonesia. Muslim women shared experience related to their husbands support and activities in women’s health and illness. The data from the interviews were analyzed using the Comparative Analysis for Interview (CAI). Women perceived that husbands fully supported their health by providing opportunities for activities, and reminding them about healthy food, their workloads, and family planning. Husbands actively involved when women faced health issues including sharing knowledge and experience, discussing any health problems, advising for medical check-ups, and accompanying them for treatments. The analysis also found that husbands were less active and offered less advice regarding prevention and early detection of cancer. This study highlights the significant involvement of Muslim husbands in women’s health and illness, yet a lack of support from husbands related to screening and cancer prevention. This condition could be a burden for Muslim women to participate in health programs related to cancer prevention and early detection. Health education programs to improve Muslim husbands’ understanding of women’s health is needed.

Keywords: descriptive exploratory study, Muslim husbands, Muslim women, women's health and illness

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3287 Prediction of Soil Liquefaction by Using UBC3D-PLM Model in PLAXIS

Authors: A. Daftari, W. Kudla

Abstract:

Liquefaction is a phenomenon in which the strength and stiffness of a soil is reduced by earthquake shaking or other rapid cyclic loading. Liquefaction and related phenomena have been responsible for huge amounts of damage in historical earthquakes around the world. Modelling of soil behaviour is the main step in soil liquefaction prediction process. Nowadays, several constitutive models for sand have been presented. Nevertheless, only some of them can satisfy this mechanism. One of the most useful models in this term is UBCSAND model. In this research, the capability of this model is considered by using PLAXIS software. The real data of superstition hills earthquake 1987 in the Imperial Valley was used. The results of the simulation have shown resembling trend of the UBC3D-PLM model.

Keywords: liquefaction, plaxis, pore-water pressure, UBC3D-PLM

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3286 Establishment of a Nomogram Prediction Model for Postpartum Hemorrhage during Vaginal Delivery

Authors: Yinglisong, Jingge Chen, Jingxuan Chen, Yan Wang, Hui Huang, Jing Zhnag, Qianqian Zhang, Zhenzhen Zhang, Ji Zhang

Abstract:

Purpose: The study aims to establish a nomogram prediction model for postpartum hemorrhage (PPH) in vaginal delivery. Patients and Methods: Clinical data were retrospectively collected from vaginal delivery patients admitted to a hospital in Zhengzhou, China, from June 1, 2022 - October 31, 2022. Univariate and multivariate logistic regression were used to filter out independent risk factors. A nomogram model was established for PPH in vaginal delivery based on the risk factors coefficient. Bootstrapping was used for internal validation. To assess discrimination and calibration, receiver operator characteristics (ROC) and calibration curves were generated in the derivation and validation groups. Results: A total of 1340 cases of vaginal delivery were enrolled, with 81 (6.04%) having PPH. Logistic regression indicated that history of uterine surgery, induction of labor, duration of first labor, neonatal weight, WBC value (during the first stage of labor), and cervical lacerations were all independent risk factors of hemorrhage (P <0.05). The area-under-curve (AUC) of ROC curves of the derivation group and the validation group were 0.817 and 0.821, respectively, indicating good discrimination. Two calibration curves showed that nomogram prediction and practical results were highly consistent (P = 0.105, P = 0.113). Conclusion: The developed individualized risk prediction nomogram model can assist midwives in recognizing and diagnosing high-risk groups of PPH and initiating early warning to reduce PPH incidence.

Keywords: vaginal delivery, postpartum hemorrhage, risk factor, nomogram

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3285 Glyco-Biosensing as a Novel Tool for Prostate Cancer Early-Stage Diagnosis

Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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3284 Comparison the Effectiveness of Pain Cognitive- Behavioral Therapy and Its Computerized Version on Reduction of Pain Intensity, Depression, Anger and Anxiety in Children with Cancer: A Randomized Controlled Trial

Authors: Najmeh Hamid, Vajiheh Hamedy , Zahra Rostamianasl

Abstract:

Background: Cancer is one of the medical problems that have been associated with pain. Moreover, the pain is combined with negative emotions such as anxiety, depression and anger. Poor pain management causes negative effects on the quality of life, which results in negative effects that continue a long time after the painful experiences. Objectives: The aim of this research was to compare the effectiveness of Common Cognitive Behavioral Therapy for Pain and its computerized version on the reduction of pain intensity, depression, anger and anxiety in children with cancer. Methods: The research method of this “Randomized Controlled Clinical Trial” was a pre, post-test and follow-up with a control group. In this research, we have examined the effectiveness of Common Cognitive Behavioral Therapy for Pain and its computerized version on the reduction of pain intensity, anxiety, depression and anger in children with cancer in Ahvaz. Two psychological interventions (cognitive behavioral therapy for pain and the computerized version) were compared with the control group. The sample consisted of 60 children aged 8 to 12 years old with different types of cancer at Shafa hospital in Ahwaz. According to the including and excluding criteria such as age, socioeconomic status, clinical diagnostic interview and other criteria, 60 subjects were selected. Then, randomly, 45 subjects were selected. The subjects were randomly divided into three groups of 15 (two experimental and one control group). The research instruments included Spielberger Anxiety Inventory (STAY-2) and International Pain Measurement Scale. The first experimental group received 6 sessions of cognitive-behavioral therapy for 6 weeks, and the second group was subjected to a computerized version of cognitive-behavioral therapy for 6 weeks, but the control group did not receive any interventions. For ethical considerations, a version of computerized cognitive-behavioral therapy was provided to them. After 6 weeks, all three groups were evaluated as post-test and eventually after a one-month follow-up. Results: The findings of this study indicated that both interventions could reduce the negative emotions (pain, anger, anxiety, depression) associated with cancer in children in comparison with a control group (p<0.0001). In addition, there were no significant differences between the two interventions (p<0.01). It means both interventions are useful for reducing the negative effects of pain and enhancing adjustment. Conclusion: we can use CBT in situations in which there is no access to psychologists and psychological services. In addition, it can be a useful alternative to conventional psychological interventions.

Keywords: pain, children, psychological intervention, cancer, anger, anxiety, depression

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3283 Impact of Twin Therapeutic Approaches on Certain Biophysiological Parameters among Breast Cancer Patients after Breast Surgery at Selected Hospital

Authors: Selvia Arokiya Mary

Abstract:

Introduction: Worldwide, breast cancer comprises 10.4% of all cancer incidence among women. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Many women who undergo breast surgery suffer from ill-defined pain syndromes. STATEMENT OF THE PROBLEM: A study to assess the effectiveness of twin therapeutic approaches on certain bio-physiological parameters in breast cancer patients after breast surgery at selected hospital, Chennai. Objectives: This study is to 1. assess the level of certain biophysiological parameters in women after mastectomy. 2. assess the effectiveness of twin therapeutic approaches on certain biophysiological parameters in women after mastectomy. 3. correlate the practice of twin therapeutic approaches with certain biophysiological parameters. 4. associate the selected demographic variables with certain biophysiological parameters in women after mastectomy Research Design and Method: Pre experimental research design was used. Fifty women were selected by using convenient sampling technique at government general hospital, Chennai. Results: The Level of pain shows, in the study group 49(98%) of them had moderate in the pre test and after the intervention all of them had mild pain in the post test. In relation to level of shoulder function before the intervention shows that in the study group 49(98%) of them had movement towards gravity and after intervention 24 (48%) of them had movement against gravity maximum resistance. There was a significant reduction in pain and shoulder stiffness level at a ‘P’ level of < 0.001. There was a negative correlation between the pranayama practice and the level of pain, there was a positive correlation between the arm exercise practice and the level of shoulder function. There was no significant association between demographic and clinical variables with the level of pain and shoulder function in the study. Hypothesis: There is a significant difference in level of pain and shoulder function among women following breast surgery who receive pranayama & arm exercise programme. The pranayama had effect in terms of reduction of pain, arm exercise programme had effect in prevention of arm stiffness among post operative women following breast surgery. Thus the stated hypothesis was accepted. Conclusion: On the basis of the findings of the present study there was Advancing age related to increasing risk of breast cancer, level of pain also the type of surgery was associated with level of pain and shoulder function, There fore it is to be concluded that the study participants may get benefited by practice of pranayama and arm exercise program.

Keywords: biophysiological parameters breast surgery, lumpectomy , mastectomy, radical mastectomy, twin therapeutic approach, pranayama, arm exercise

Procedia PDF Downloads 241
3282 Evaluation of Machine Learning Algorithms and Ensemble Methods for Prediction of Students’ Graduation

Authors: Soha A. Bahanshal, Vaibhav Verdhan, Bayong Kim

Abstract:

Graduation rates at six-year colleges are becoming a more essential indicator for incoming fresh students and for university rankings. Predicting student graduation is extremely beneficial to schools and has a huge potential for targeted intervention. It is important for educational institutions since it enables the development of strategic plans that will assist or improve students' performance in achieving their degrees on time (GOT). A first step and a helping hand in extracting useful information from these data and gaining insights into the prediction of students' progress and performance is offered by machine learning techniques. Data analysis and visualization techniques are applied to understand and interpret the data. The data used for the analysis contains students who have graduated in 6 years in the academic year 2017-2018 for science majors. This analysis can be used to predict the graduation of students in the next academic year. Different Predictive modelings such as logistic regression, decision trees, support vector machines, Random Forest, Naïve Bayes, and KNeighborsClassifier are applied to predict whether a student will graduate. These classifiers were evaluated with k folds of 5. The performance of these classifiers was compared based on accuracy measurement. The results indicated that Ensemble Classifier achieves better accuracy, about 91.12%. This GOT prediction model would hopefully be useful to university administration and academics in developing measures for assisting and boosting students' academic performance and ensuring they graduate on time.

Keywords: prediction, decision trees, machine learning, support vector machine, ensemble model, student graduation, GOT graduate on time

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3281 Synthesis and Biological Activity Evaluation of U Complexes

Authors: Mohammad Kazem Mohammadi

Abstract:

The use of anticancer agents forms an important part of the treatment of cancer of various types. Uranyl Complexes with DPHMP ligand have been used for the prevention and treatment of cancers. U(IV) metal complexes prepared by reaction of uranyl salt UO2 (NO3)2.6H2O with DPHMP in dry acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1H NMR, 13C NMR and UV–Visible spectroscopy. These new complex showed excellent antitumor activity against two kinds of cancer cells that that are HT29:Haman colon adenocarcinoma cell line and T47D:human breast adenocarcinoma cell line.

Keywords: uranyl complexes, DPHMP ligand, antitumor activity, HT29, T47D

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3280 Selecting the Best RBF Neural Network Using PSO Algorithm for ECG Signal Prediction

Authors: Najmeh Mohsenifar, Narjes Mohsenifar, Abbas Kargar

Abstract:

In this paper, has been presented a stable method for predicting the ECG signals through the RBF neural networks, by the PSO algorithm. In spite of quasi-periodic ECG signal from a healthy person, there are distortions in electro cardiographic data for a patient. Therefore, there is no precise mathematical model for prediction. Here, we have exploited neural networks that are capable of complicated nonlinear mapping. Although the architecture and spread of RBF networks are usually selected through trial and error, the PSO algorithm has been used for choosing the best neural network. In this way, 2 second of a recorded ECG signal is employed to predict duration of 20 second in advance. Our simulations show that PSO algorithm can find the RBF neural network with minimum MSE and the accuracy of the predicted ECG signal is 97 %.

Keywords: electrocardiogram, RBF artificial neural network, PSO algorithm, predict, accuracy

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3279 Clinical Value of 18F-FDG-PET Compared with CT Scan in the Detection of Nodal and Distant Metastasis in Urothelial Carcinoma or Bladder Cancer

Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

Abstract:

Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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3278 Managing Incomplete PSA Observations in Prostate Cancer Data: Key Strategies and Best Practices for Handling Loss to Follow-Up and Missing Data

Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

Abstract:

Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

Procedia PDF Downloads 78
3277 Equivalent Circuit Representation of Lossless and Lossy Power Transmission Systems Including Discrete Sampler

Authors: Yuichi Kida, Takuro Kida

Abstract:

In a new smart society supported by the recent development of 5G and 6G Communication systems, the im- portance of wireless power transmission is increasing. These systems contain discrete sampling systems in the middle of the transmission path and equivalent circuit representation of lossless or lossy power transmission through these systems is an important issue in circuit theory. In this paper, for the given weight function, we show that a lossless power transmission system with the given weight is expressed by an equivalent circuit representation of the Kida’s optimal signal prediction system followed by a reactance multi-port circuit behind it. Further, it is shown that, when the system is lossy, the system has an equivalent circuit in the form of connecting a multi-port positive-real circuit behind the Kida’s optimal signal prediction system. Also, for the convenience of the reader, in this paper, the equivalent circuit expression of the reactance multi-port circuit and the positive- real multi-port circuit by Cauer and Ohno, whose information is currently being lost even in the world of the Internet.

Keywords: signal prediction, pseudo inverse matrix, artificial intelligence, power transmission

Procedia PDF Downloads 119
3276 Experiencing Scarred Body among Thai Women Living with Breast Cancer

Authors: Dusanee Suwankhong, Pranee Liamputtong

Abstract:

Breast surgery leaves undesirable scars to all women who experienced mastectomy, despite the fact that this could be a principle approach to save one life. This paper explores how Thai women living with breast cancer perceived and experienced a scarred body after breast surgery. In-depth interviews and drawing methods were employed among 20 women diagnosed with breast cancer. The interviewed data were analysed using thematic analysis method. The results showed that all women with breast cancer who underwent breast surgery perceived and experienced scar as a persisting and visible side-effect. This disfigurement appearance presented a negative image of feminine identity and led to emotional burdens among women. They responded to being scarred in different ways relating to their perceptions of body and changes. The older group had less embarrassed feelings towards being scarred comparing to the younger one. All women tried to seek means to cope with such physical impairment and keep balance life related to their condition. For example, they relied on Buddhism practice and tried to heal the keloid using natural products. Scars appeared to be an unpleasant effect for women who underwent breast mastectomy. Nurses and health care professionals in the local health service sectors need to pay close attention to how the women see the scarred body and their experiences of living with the distorted feminine appearance, and to provide sensitive support that meets the needs of these vulnerable women. The suitable supports can reduce the sense of embarrassment and increase their sense of self-confidence about their social femininity.

Keywords: breast surgery, emotional response, qualitative study, scars, Thai women

Procedia PDF Downloads 162
3275 A Neural Network System for Predicting the Hardness of Titanium Aluminum Nitrite (TiAlN) Coatings

Authors: Omar M. Elmabrouk

Abstract:

The cutting tool, in the high-speed machining process, is consistently dealing with high localized stress at the tool tip, tip temperature exceeds 800°C and the chip slides along the rake face. These conditions are affecting the tool wear, the cutting tool performances, the quality of the produced parts and the tool life. Therefore, a thin film coating on the cutting tool should be considered to improve the tool surface properties while maintaining its bulks properties. One of the general coating processes in applying thin film for hard coating purpose is PVD magnetron sputtering. In this paper, the prediction of the effects of PVD magnetron sputtering coating process parameters, sputter power in the range of (4.81-7.19 kW), bias voltage in the range of (50.00-300.00 Volts) and substrate temperature in the range of (281.08-600.00 °C), were studied using artificial neural network (ANN). The results were compared with previously published results using RSM model. It was found that the ANN is more accurate in prediction of tool hardness, and hence, it will not only improve the tool life of the tool but also significantly enhances the efficiency of the machining processes.

Keywords: artificial neural network, hardness, prediction, titanium aluminium nitrate coating

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3274 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

Abstract:

Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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3273 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment

Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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3272 Anti-Cancerous Activity of Sargassum siliquastrum in Cervical Cancer: Choreographing the Fly's Danse Macabre

Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

Abstract:

Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

Procedia PDF Downloads 625
3271 The Role of Micro-Ribonucleic Acid-182 and Micro-Ribonucleic Acid-214 in Cisplatin Resistance of Triple-Negative Breast Cancer Cells

Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul

Abstract:

Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.

Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX

Procedia PDF Downloads 123