Search results for: nonsmall cell lung cancer

Authors: Robert P. Dufresne, Hamid Arabzadeh

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The current study investigates the effectiveness of a new form of permanent baseboard insulators with an umbrella action, hereinafter referred to as Coronary Insulator, in supporting and protecting the assembly of electrodes immersed in an electrolytic cell and in increasing the lifespan of the lateral sides of the electrolytic cell, in both electro-winning and electro-refinery method. The advantages of using a coronary insulator in addition to the top capping board (equipotential insulator) were studied compared to the conventional assembly of an electrolytic cell. Then, a thermal imaging technique was utilized during high-temperature thermal (heat transfer) tests for sample cell walls with and without coronary insulators in their assembly to show the effectiveness of coronary insulators in protecting the cell wall under extreme conditions. It was shown that, unlike the conventional assembly, which is highly prone to damages to the cell wall under thermal shocks, the presence of coronary insulator can significantly increase the level of protection of the cell due to their ultra-high thermal and chemical resistance, as well as decreasing the replacement frequency of insulators to almost zero. Besides, the results of the study showed that the test assembly with the coronary insulator provides better consistency in positioning and, subsequently, better contact, compared to the conventional method, which reduces the chance of electric short-circuit in the system.

Keywords: capping board, coronary insulator, electrolytic cell, thermal shock.

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Authors: Seyedeh Sepideh Amini, Navideh Aghaei Amirkhizi, Seyedeh Paniz Amini, Seyed Soheil Sayyahi, Mohammad Reza Davar Panah

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CT-Scan is one of the lateral and sectional imaging methods that produce 3D-images with use of rotational x-ray tube around central axis. This study is about evaluation and calculation of effective doses around heart organs such as breast, lung and liver with CT-Scan 128 dual sources with TLD_100 and RANDO Phantom by spiral, flash and conventional protocols. In results, it is showed that in spiral protocol organs have maximum effective dose and minimum in flash protocol. Thus flash protocol advised for children and risk persons.

Keywords: X-ray computed tomography, dosimetry, TLD-100, RANDO, phantom

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Authors: Djaafar Fatiha, Ghalem Bachir, Hadri Bagdad

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We studied mainly the influence of temperature, thickness, molar fraction and the doping of the various layers (emitter, base, BSF and window) on the performances of a photovoltaic solar cell. In a first stage, we optimized the performances of the InGaP/GaAs dual-junction solar cell while varying its operation temperature from 275°K to 375 °K with an increment of 25°C using a virtual wafer fabrication TCAD Silvaco. The optimization at 300 °K led to the following result: Icc =14.22 mA/cm2, Voc =2.42V, FF=91.32 %, η= 22.76 % which is close with those found in the literature. In a second stage ,we have varied the molar fraction of different layers as well their thickness and the doping of both emitters and bases and we have registered the result of each variation until obtaining an optimal efficiency of the proposed solar cell at 300°K which was of Icc=14.35mA/cm2,Voc=2.47V,FF=91.34,and η=23.33% for In(1-x)Ga(x)P molar fraction( x=0.5).The elimination of a layer BSF on the back face of our cell, enabled us to make a remarkable improvement of the short-circuit current (Icc=14.70 mA/cm2) and a decrease in open circuit voltage Voc and output η which reached 1.46V and 11.97% respectively. Therefore, we could determine the critical parameters of the cell and optimize its various technological parameters to obtain the best performance for a dual junction solar cell .This work opens the way with new prospects in the field of the photovoltaic one. Such structures will thus simplify the manufacturing processes of the cells; will thus reduce the costs while producing high outputs of photovoltaic conversion.

Keywords: modeling, simulation, multijunction, optimization, Silvaco ATLAS

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Authors: S. Tebibel, R. L. Bouchouka, C. Mechati, S. Messaoudi

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The stomach cancer or gastric cancer is an aggressive cancer with a significant geographic disparity. The decrease in frequency is attributed to refrigeration, which has several beneficial consequences, increased consumption of fresh fruits and vegetables, reduced consumption of salt, which was widely used as a food preservative, and less contamination of food by carcinogenic compounds. The infection with Helicobacter pylori is responsible for progressive inflammatory changes in the gastric mucosa usually evolving into stomach cancer in 80% of cases. Methodology: This epidemiological and analytical study concerns 65 patients (46 men and 19 women) with gastric adenocarcinomas with an average age of 56.5 years and a male predominance with a sex ratio of 2.4. Results and Discussion: In this series, the clinical symptoms are dominated by epigastralgia (72.31%), vomiting (27,69%), and slimming (24,62%). The FOGD (Oeso-Gastro Duodenal Fibroscopy) performed in the 65 patients revealed a predominance of the antro-pyloric localization in 19 cases (i.e., 29.23%) and anulcerative budding appearance in 33 subjects (50,77%). Histologically, the moderately differentiated adenocarcinoma is found in 30.77% of patients, followed by well differentiated adenocarcinoma with 26.15% of patients. The immunohistochemical study revealed a positive labeling of half of the T cells by anti-CD3 AC, and a positive labeling of anti-CD20 AC in a diffuse and intense manner, with the presence of CD20-positive lymphoepithelial lesions compatible with CD20 a low grade MALT non-Hodgkin's lymphoma. Conclusion: This framework of analysis revealed some risk factors for gastric cancer, such as food, hygiene, Helicobacter pylori infection, smoking and family history.

Keywords: cancer, Helicobacter pylori, immunohistochemistry, stomach

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Merfat Algethami, Anton Blencowe, Bryce Feltis, Stephen Best, Moshi Geso

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Nano-materials with high atomic number atoms have been demonstrated to enhance the effective radiation dose and thus potentially could improve therapeutic efficacy in radiotherapy. The optimal nanoparticulate agents require high X-ray absorption coefficients, low toxicity, and should be cost effective. The focus of our research is the development of a nanoparticle therapeutic agent that can be used in radiotherapy to provide optimal enhancement of the radiation effects on the target. In this study, we used bismuth (Bi) nanoparticles coated with starch and bismuth sulphide nanoparticles (Bi2S3) coated with polyvinylpyrrolidone (PVP). These NPs are of low toxicity and are one of the least expensive heavy metal-based nanoparticles. The aims of this study were to synthesise Bi2S3 and Bi NPs, and examine their cytotoxicity to human lung adenocarcinoma epithelial cells (A549). The dose enhancing effects of NPs on A549 cells were examined at both KV and MV energies. The preliminary results revealed that bismuth based nanoparticles show increased radio-sensitisation of cells, displaying dose enhancement with KV X-ray energies and to a lesser degree for the MV energies. We also observed that Bi NPs generated a greater dose enhancement effect than Bi2S3 NPs in irradiated A549 cells. The maximum Dose Enhancement Factor (DEF) was obtained at lower energy KV range when cells treated with Bi NPs (1.5) compared to the DEF of 1.2 when cells treated with Bi2S3NPs. Less radiation dose enhancement was observed when using high energy MV beam with higher DEF value of Bi NPs treatment (1.26) as compared to 1.06 DEF value with Bi2S3 NPs. The greater dose enhancement was achieved at KV energy range, due the effect of the photoelectric effect which is the dominant process of interaction of X-ray. The cytotoxic effect of Bi NPs on enhancing the X-ray dose was higher due to the higher amount of elemental Bismuth present in Bi NPs compared to Bi2S3 NPs. The results suggest that Bismuth based NPs can be considered as valuable dose enhancing agents when used in clinical applications.

Keywords: A549 lung cancer cells, Bi2S3 nanoparticles, dose enhancement effect, radio-sensitising agents

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Authors: Betzabet García-Mendoza, Rocío Abascal-Mena

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Breast and cervical cancer are among the leading causes of death of women in Mexico. The mortality rate for these diseases is alarming, even though there have been many campaigns for making people self-aware of the importance of conducting gynecological studies for a timely prevention and detection, these have not been enough. This paper presents a mobile application for organizing and controlling gynecological studies in order to help and boost women to take care of their bodies and health. The process of analyzing and designing the mobile application is presented, along with all the steps carried out by following a user-centered design methodology.

Keywords: breast cancer, cervical cancer, gynecological mobile application, paper prototyping, storyboard, women health

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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Authors: Mona Nada, Fahmy Fahmy

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Background: Pleomorphic dermal sarcoma is a rare form of skin cancer affecting cutaneous layer and, in some cases associated with recurrence and metastasis, very commonly to seen in elderly patient affecting the area of head and neck. Pleomorphic dermal sarcoma rises in ultraviolet light exposed areas. The symptoms and severity of this kind of skin cancer varies according to histological factors. The differentiation of Pleomorphic dermal sarcoma needs extensive immunohistochemistry, as the diagnosis depends mainly on exclusion to rule out other malignancy like poorly differentiated squamous cell carcinoma, melanoma, angiosarcoma and leiomyosarcoma. Objective: assessing the management of Pleomorphic dermal sarcoma in our unit and compared to the updated guidelines. Design: Retrospective study Collection of patient data from medical records at countess of Chester plastic surgery unit of the last 5 years, all histologically confirmed Pleomorphic dermal sarcoma (2017-2023). Data were collected confirmed to be Pleomorphic dermal sarcoma were included in the study. The data collected: clinical description of the lesions at first presentation, operation time, multidisciplinary team discussion, plan, referral as well as second operation and investigation done. With comparison of histological examination, immunohistochemistry staining, the excision and rate of recurrence. Results: data collected N19 from (2017-2023) showed the disease predominantly affecting males and the lesion mainly in head and neck, the diagnosis needed extensive immunohistochemistry to differentiate between other malignancy. recurrence present in numbers of the cases which managed after multidisciplinary team discussion either by excision or radiotherapy. Conclusion: Pleomorphic dermal sarcoma is a rare malignancy which needs more understanding and avoid missing as it is aggressive form of skin cancer, there is a chance of metastasis and recurrence which makes it very important to understand the process of development of the cancer and frequent review of the management guidelines.

Keywords: pleomorphic dermal sarcoma, recurrence, radiotherapy, surgical

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Jacklynn Walters, Amanda A. Alblas, Linda M. Greyling

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Cervical carcinoma is the second most common cancer found in women. Diagnosis of skeletal metastases is uncommon in cervical cancer patients. The aim of this study was to determine the prevalence of skeletal metastases in in a Western Cape skeletal population. Skeletal samples (n=14) from the Kirsten Skeletal Collection at Stellenbosch University, diagnosed pre-mortem with cervical cancer, were examined. Macroscopic analysis was done using low magnification to examine each skeletal element for signs of disease. Skeletons were also x-rayed using the Lodox® Statscan® Imaging system and the scans evaluated by a musculoskeletal radiologist. Three (21%) of the skeletons showed metastases, with the os coxae and lower vertebral column affected in all three cases. Furthermore, metastases occurred in the scapulae and ribs in two of the cases and in one case the skull, mandible, and long bones were affected. Additionally, three skeletons without evidence of skeletal metastases presented with a periosteal reaction on the os coxae in response to the diseased adjacent soft tissue. Previous studies observed that skeletal metastases are more common than what is diagnosed pre-mortem with the vertebral spine most commonly affected. The findings of this study agree with previous reports and illustrate the effectiveness of the Lodox® scanner in diagnoses of metastases in skeletal material.

Keywords: cancer, cervix, radiology, skeletal metastases

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Authors: Aref Aasi, Sahar Ebrahimi Bajgani, Erfan Aasi

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Breast cancer (BC) continues to be the most frequent cancer in females and causes the highest number of cancer-related deaths in women worldwide. Inspired by recent advances in studying the relationship between different patient attributes and features and the disease, in this paper, we have tried to investigate the different classification methods for better diagnosis of BC in the early stages. In this regard, datasets from the University Hospital Centre of Coimbra were chosen, and different machine learning (ML)-based and neural network (NN) classifiers have been studied. For this purpose, we have selected favorable features among the nine provided attributes from the clinical dataset by using a random forest algorithm. This dataset consists of both healthy controls and BC patients, and it was noted that glucose, BMI, resistin, and age have the most importance, respectively. Moreover, we have analyzed these features with various ML-based classifier methods, including Decision Tree (DT), K-Nearest Neighbors (KNN), eXtreme Gradient Boosting (XGBoost), Logistic Regression (LR), Naive Bayes (NB), and Support Vector Machine (SVM) along with NN-based Multi-Layer Perceptron (MLP) classifier. The results revealed that among different techniques, the SVM and MLP classifiers have the most accuracy, with amounts of 96% and 92%, respectively. These results divulged that the adopted procedure could be used effectively for the classification of cancer cells, and also it encourages further experimental investigations with more collected data for other types of cancers.

Keywords: breast cancer, diagnosis, machine learning, biomarker classification, neural network

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

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N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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Authors: Mai Ashraf Talaat

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Objectives: The aim of this review article is to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy and to evaluate the risk of developing bisphosphonate-related osteonecrosis of the jaw following dental implant surgery. Materials and Methods: A thorough search was conducted, with no time or language restriction, using: PubMed, PubMed Central, Web of Science, and ResearchGate electronic databases. Medical Subject Headings (MeSH) terms such as “bisphosphonate”, “dental implant”, “bisphosphonate-related osteonecrosis of the jaw (BRONJ)”, “osteonecrosis”, “breast cancer, MRONJ”, and their related entry terms were used. Eligibility criteria included studies and clinical trials that evaluated the impact of bisphosphonates on dental implants. Conclusion: Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered. More randomized controlled trials with long-term follow-ups are needed to draw more evidence-based conclusions.

Keywords: dental implants, breast cancer, bisphosphonates, osteonecrosis, bisphosphonate-related osteonecrosis of the jaw

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Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

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Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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Authors: C. Soh, S. Muktar, C. M. Malata, J. R. Benson

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Introduction Reasons for requesting CPM include prevention of recurrence, peace of mind and moving on after breast cancer. Some women seek CPM as a delayed procedure but factors influencing this are poorly understood. Methods A retrospective analysis examined patients undergoing CPM as either an immediate or delayed procedure with or without breast reconstruction (BR) between January 2009 and December 2019. A cross-sectional survey based on validated questionnaires (5 point Likert scale) explored patients’ decision-making process in terms of timing of CPM and any BR. Results A total of 123 patients with unilateral breast cancer underwent CPM with 39 (32.5%) delayed procedures with or without BR. The response rate amongst patients receiving questionnaires (n=33) was 22/33 (66%). Within this delayed CPM cohort were three reconstructive scenarios 1) unilateral immediate BR with CPM (n=12); 2) delayed CPM with concomitant bilateral BR (n=22); 3) delayed bilateral BR after delayed CPM (n=3). Two patients had delayed CPM without BR. The most common reason for delayed CPM was to complete all cancer treatments (including radiotherapy) before surgery on the unaffected breast (score 2.91). The second reason was unavailability of genetic test results at the time of therapeutic mastectomy (score 2.64) whilst the third most cited reason was a subsequent change in family cancer history. Conclusion Factors for delayed CPM are patient-driven with few women spontaneously changing their mind having initially decided against immediate CPM for reasons also including surgical duration. CPM should be offered as a potentially delayed option with informed discussion of risks and benefits.

Keywords: Breast Cancer, CPM, Prophylactic, Rationale

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Authors: Farhad Forouharmajd, Hossein Ebrahimi, Siamak Pourabdian

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Introduction: Prevalent use of cell phones (mobile phones) has led to increasing worries about the effect of radiofrequency waves on the physiology of human body. This study was done to determine different reactions of the temperatures in different depths of brain tissue in confronting with radiofrequency waves of cell phones. Methodology: This study was an empirical research. A cow's brain tissue was placed in a compartment and the effects of radiofrequency waves of the cell phone was analyzed during confrontation and after confrontation, in three different depths of 2, 12, and 22 mm of the tissue, in 4 mm and 4 cm distances of the tissue to a cell phone, for 15 min. Lutron thermometer was used to measure the tissue temperatures. Data analysis was done by Lutron software. Findings: The rate of increasing the temperature at the depth of 22 mm was higher than 2 mm and 12mm depths, during confrontation of the brain tissue at the distance of 4 mm with the cell phone, such that the tissue temperatures at 2, 12, and 22 mm depths increased by 0.29 ˚C, 0.31 ˚C, and 0.37 ˚C, respectively, relative to the base temperature (tissue temperature before confrontation). Moreover, the temperature of brain tissue at the distance of 4 cm by increasing the tissue depth was more than other depths. Increasing the tissue temperature also existed by increasing the brain tissue depth after the confrontation with the cell phone. The temperature of the 22 mm depth increased with higher speed at the time confrontation. Conclusion: Not only radiofrequency waves of cell phones increased the tissue temperature in all the depths of the brain tissue, but also the temperature due to radiofrequency waves of the cell phone was more at the depths higher than 22 mm of the tissue. In fact, the thermal effect of radiofrequency waves was higher in higher depths.

Keywords: mobile phone, radio frequency waves, brain tissue, temperature

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Authors: Abdullah Saeidi, Aydin Gülses, Christan Flörke

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Skin cancer of the face region is the most common type of malignancy and surgical excision is the preferred approach. However, the clinical long term results reported in the literature are still controversial. Objectives: To describe; 1. Demographical characteristics 2. Affected site, distribution and TNM classification regarding tumor type 3. Surgical aspects • Surgical removal: excision principles, safety margins, the need for secondary resection, primary reconstruction/ defect closure, anesthesia protocol, duration of hospital stay (if any) • Secondary intervention for defect closure/reconstruction: Flap technique, anesthesia protocol, duration of hospital stay (if any), postoperative wound management etc. 4. Tumor recurrences 5. Clinical outcomes 6. Studying the possible therapy approach throw Biostatistical relation and correlation between multiple Histological, diagnostics and clinical Faktors. following surgical ablation of the skin cancer of the head and neck region. Methods: Selection and statistical analysis of medical records of patients who had admitted to the Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig Holstein, Campus Kiel during the period of 2015-2019 will be retrospectively evaluated. Data will be collected via ORBIS Information-Management-System (ORBIS AG, Saarbrücken, Germany).

Keywords: non melanoma skin cancer, face skin cancer, skin reconstruction, non melanoma skin cancer recurrence, non melanoma skin cancer metastases

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Authors: Nuhi Arslani, Stojan Potrc, Timotej Mikuljan

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Background: In Department of Abdominal and General Surgery of University Medical Centre Maribor, we treated 578 patients for rectal cancer between 2004 and 2014. During and after treatment we especially concentrated on monitoring local and systemic complications. Methods: For analysis, we used data gathered from preoperative diagnostic tests, reports gathered during operation, reports from the pathohistologic review, and reports on complications after surgery and follow up. Results: In the case of 573 (out of 578) patients (99.1%) we performed resection. R0 was achieved in 551 patients (96,1%). R1 was achieved in 8 patients (1,4%). R2 was achieved in 14 patients (2,4%). Local complications were reported in 78 (13.5%) patients and systemic complications were reported in 68 (11.7%). We would like to point out the low number of local and systemic complications. Conclusions: With advances in surgical techniques, with a multimodal-multidisciplinary approach and with the use of total mesorectal excision we experienced a significant improvement in reducing the number of local and systemic complications in patients with rectal cancer. However, there still remains the question for truly optimal care for each patient with rectal cancer and his quality of life after surgical treatment.

Keywords: local complications, rectal cancer, resection, systemic complications

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Authors: Mazouz Halima, Belghachi Abdrahmane

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Effects of electron irradiation-induced deep level defects have been studied on both n/p and p/n indium phosphide solar cells with very thin emitters. The simulation results show that n/p structure offers a somewhat better short circuit current but the p/n structure offers improved circuit voltage, not only before electron irradiation, but also after 1MeV electron irradiation with 5.1015 fluence. The simulation also shows that n/p solar cell structure is more resistant than that of p/n structure.

Keywords: InP solar cell, p/n and n/p structure, electron irradiation, output parameters

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Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

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The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

Procedia PDF Downloads 274

Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Sally Shepherd, Craig Murphy

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Introduction: The uterus or cervix are unusual locations as metastatic sites for cancers. It is further unusual for it to be a site of metastasis, whilst the primary malignancy remains occult. Case Report: A 63-year-old female with three months of altered bowel habits underwent a CT scan of the abdomen and pelvis, revealing a bulky uterus and left ovary, nonspecific colonic thickening, and diffuse peritoneal changes. She underwent colposcopy, which revealed a large endocervical polyp that was excised, revealing strongly hormone-positive metastatic invasive lobular breast cancer. She subsequently underwent a PET scan, which showed moderately diffuse activity in the cervix and left adnexa. Breast examination was unremarkable, and screening mammography, ultrasound, and MRI of the breast did not identify any lesions. Her blood tests revealed a Ca 15-3 of 934, CA-125 of 220, and CEA of 27. She was commenced on letrozole and ribociclib with an improvement in her symptoms. Conclusion: It is rare for occult breast cancer to be established and diagnosed by pelvic imaging and biopsy. Suspicion of uterine or cervical metastasis should be heightened in patients with an active or past history of breast cancer.

Keywords: occult breast cancer, cervical metastasis, invasive lobular carcinoma, metastasis

Procedia PDF Downloads 115