Search results for: breast cancer staging

Authors: Geovanna dos Santos Romeiro, Polintia Rayza Brito da Silva, Luis Henrique Moura, Izadora Moreira Do Amaral, Marília Vitória Pinto Milhomem

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Introduction: The nose is one of the most likely sites for the appearance of malignancy on the face. This can be associated with its unique position of exposure to environmental damage, lack of photoprotection and because it is an area susceptible to greater sun exposure. It is already known that the most common type of nasal tumor is basal cell carcinoma. Squamous cell carcinoma is less common but considerably more aggressive, with a tendency to grow rapidly and metastasize. Nasal skin cancer can have a good prognosis, regardless of the type of treatment chosen, i.e., surgery, radiotherapy or electrodissection. However, tumors that are not diagnosed and treated quickly can be harmful and have a greater chance of metastasizing. When curative surgery is performed, therapies and reconstructive surgical procedures are usually required. Objective: The objective is to review the literature on nasal skin tumors and their types and specific locations. Forty-four articles published in Pubmed related to the location of skin cancer in the specific nasal areas region were analyzed. Twelve were excluded for being prior to the year 2000, three with inconclusive results, and one with unbiased conclusions. Results and Conclusion: Regarding the prevalence of types of nasal tumors, basal cell carcinoma comprises the majority, occurring predominantly in the ala, tip and root; squamous cell carcinoma, on the other hand, is more common in the lateral borders and columella. Even so, 2 articles report that the prevalence of metastasis has a higher incidence in squamous cell carcinomas. All of this points to the importance of early location, including regions that are often overlooked in the examination if the patient is wearing glasses. This topic needs further investigation for a greater correlation between anatomy and clinical-surgical implications.

Keywords: skin cancer, melanoma, non-melanoma, surgery

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Authors: Elida Tafupenji Kamanga

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Cancer of the cervix remains one of the high causes of death among Malawian women. Despite the government introduction of free screening services throughout the country, patronage still remains low and lack of knowledge high. Given the critical role mass media plays in relaying different information to the public including health and its influence on health behaviours, the study sought to analyse Malawi media coverage of the disease and its effectiveness. The findings of the study will help inform media advocacy directed at changing any coverage impeding the effective dissemination of cervical cancer message which consequently will help increase awareness and accessing of screening behaviours among women. A content analysis of 29 newspapers and promotional messages on cervical from a local radio station was conducted for the period from 2012 to 2015. Overall the results showed media coverage in terms of content and frequency increased for the four-year period. However, of concern was the quality of information both media presented to the public. The lapse in information provided means there is little education taking place through the media which could be contributing to the knowledge gap the women have thereby affecting their decision to screen. Also lack of adequate funding to media institutions and lack of collaboration between media institutions and stakeholders involved in the fight against the disease were noted as other contributing factors to low coverage of the disease. Designing messages that are not only informative and educative but also innovative may help increase awareness; improve the knowledge gap and potential adoption of preventive screening behaviour by Malawian women. Conversely, good communication between the media institutions and researchers involved in the fight against the disease through the channelling of new findings back to the public as well as increasing funding towards similar cause should be considered.

Keywords: cervical cancer, effectiveness, media coverage, screening

Procedia PDF Downloads 197

Authors: Fatma Koksal Çakirlar, Si̇nem Ozdemir, Selcan Akyol, Revazi̇ye Gulesen, Murat Gunaydin, Nevri̇ye Gonullu, Belkis Levent, Nuri̇ Kiraz

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Vibrio cholerae O1 and O139 are the causative agent of epidemic or pandemic cholera. V. cholerae O1 is generally accepted as a non-invasive enterotoxigenic organism causing gastroenteritis of various severities. Non-O1 V. cholerae can cause small outbreaks of diarrhea due to consumption of contaminated food and water. Particularly, the patients with achlorydria have a risk for vibrio infections. There are numerous case reports of bacteremia caused by vibrio in patients with predisposing conditions like cirrhosis, nephrotic syndrome, diabetes, hematologic malignancy, gastrectomy, and AIDS. We described in this study the first case of nontoxigenic, non-01/non-O139 V. cholerae isolated from the blood culture of a 77-year-old female patient with hipertension, diabetes, coronary artery disease, gout and about 9 years ago migrated breast cancer history. The patient with complaints of shortness of breath, fever and malaise admitted to our emergency clinic were evaluated. There was no diarrhea or abdominal symptoms in the patient. No growth in her urine culture, but blood culture (BACTEC 9120 system, Becton Dickinson, USA) was positive for non-01/non-O139 V. cholerae that was identified by conventional methods and Phoenix automated system (BD Diagnostic Systems, Sparks, MD). It does not secrete the cholera toxin. The agglutination test was negative with polyvalent O1 antisera and O139 antiserum. Empirically ceftriaxone was administered to the patient and she was discharged with improvement in general condition. In this study we report bacteremia by non-01/non-O139 V. cholerae that is rare in the worldwide and first in Turkey.

Keywords: bacteremia, blood culture, immunocompromised patient, Non-O1 vibrio cholerae

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Authors: Ghasem Yazadani, Hamidreza Ahmadi, Masoud Ahmadi, Sajad Rezazadeh

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In this paper with designing and proposing a compound of a heating and cooling system has been tried to show effect of this system on preventing esophagus cancer that can be caused by hot and cold drinks such as tea, coffee and ice water. This system has been simulated mechanically by fluent software and also has been validated by experimental way and a comprehensive result has been presented. Both of solution ways show that this system can reduce or increase temperature of drink to safe very dramatically and it can be a huge step toward consuming drinks safely and also it can be efficient about time issues. The system consists of a temperature sensor and an electronic controller that has a computer program to act automatically this task. Also this system has been presented after many different simulations and has been tried to find the best one in the point view of velocity of heating and cooling.

Keywords: fluent, heat transfer, controller, esophagus cancer

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Authors: Abujnah Dukali

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Natural honey was assessed in cell culture system for its anticancer activity. Human leukemic cell line HL 60 was treated with honey and cultured for 5 days and cytotoxicity was calculated by MTT assay. Honey showed cytotoxicity with CC50 value of 174.20 µg/ml. Radical modulation activities was assessed by lipid peroxidation assay using egg lecithin. Honey showed antioxidant activity with EC50 value of 159.73 µg/ml. In addition, treatment with HL60 cells also resulted in nuclear DNA fragmentation, as seen in agarose gel electrophoresis. This is a hallmark of cells undergoing apoptosis. Confirmation of apoptosis was performed by staining the cells with Annexin V and FACS analysis. Apoptosis is an active, genetically regulated disassembly of the cell form within. Disassembly creates changes in the phospholipid content of the cytoplasmic membrane outer leaflet. Phosphatidylserine (PS) is translocated from the inner to the outer surface of the cell for phagocytic cell recognition. The human anticoagulant, annexin V, is a Ca2+-dependent phospholipid protein with a high affinity for PS. Annexin V labeled with fluorescein can identify apoptotic cells in the population It is a confirmatory test for apoptosis. Annexin V-positive cells were defined as apoptotic cells. Since honey shows both antioxidant activity and cytotoxicity at almost the same concentration, it can prevent the free radical induced cancer as prophylactic agent and kill the cancer cells by apoptotic process as a chemotherapeutic agent. Everyday intake of honey can prevent the cancer induction.

Keywords: anticancer, cells, DNA, honey

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Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

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Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

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Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

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Authors: Osama Shakeel

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The objective of the paper is to study the clinic-pathological factors, survival analyses, recurrence rate, metastatic rate, risk factors and the management of cutaneous malignant melanoma at Shaukat Khanum Memorial Cancer Hospital and Research Center. Methodology: From 2014 to 2017, all patients with a diagnosis of cutaneous malignant melanoma (CMM) were included in the study. Demographic variables were collected. Short and long term oncological outcomes were recorded. All data were entered and analyzed in SPSS version 21. Results: A total of 28 patients were included in the study. Median age was 46.5 +/-15.9 years. There were 16 male and 12 female patients. The family history of melanoma was present in 7.1% (n=2) of the patients. All patients had a mean survival of 13.43+/- 9.09 months. Lower limb was the commonest site among all which constitutes 46.4%(n=13). On histopathological analyses, ulceration was seen in 53.6% (n=15) patients. Unclassified tumor type was present in 75%(n=21) of the patients followed by nodular 21.4% (n=6) and superficial spreading 3.5%(n=1). Clark level IV was the commonest presentation constituting 46.4%(n=13). Metastases were seen in 50%(n=14) of the patients. Local recurrence was observed in 60.7%(n=17). 64.3%(n=18) lived after one year of treatment. Conclusion: CMM is a fatal disease. Although its disease of fair skin individuals, however, the incidence of CMM is also rising in this part of the world. Management includes early diagnoses and prompt management. However, mortality associated with this disease is still not favorable.

Keywords: malignant cancer of skin, cutaneous malignant melanoma, skin cancer, survival analyses

Procedia PDF Downloads 168

Authors: Marah El-Beeli, Abdullah Balkhair, Zakaryia Al Muharmi, Samir Al Adawi, Mansoor Al-Jabri, Abdullah Al Rawahi, Hazaa Al Yahyae, Eman Al Balushi, Yahya M. Al-Farsi

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The health care service and the anticancer chemotherapeutics has changed the natural history of cancer into manageable chronic disease and improve the cancer patient’s lifestyle and increase the survival time. Despite that, still, infection is the major dilemma opposing the cancer patient either because of the clinical presentation of the cancer type and impaired immune system or as a consequence of anticancer therapy. This study has been conducted to1) track changes in the epidemiology of hospital-acquired bloodstream infections among patients with malignancies in the last five years. 2) To explore the causative pathogens and 3) the outcome of HA-BSIs in patients with a different types of malignancies. An ampi-directional study (retrospective and prospective follow up) of patients with malignancies admitted at Sultan Qaboos University hospital (570-bed tertiary hospital) during the study period (from January 2015 to December 2019). The cumulative frequency and prevalence rates of HA-BSIs by patients and isolates were calculated. In addition, the cumulative frequency of participants with single versus mixed infections and types of causative micro-organisms of HA-BSIs were obtained. A total of 1246 event of HA-BSIs has occurred during the study period. Nearly the third (30.25%) of the HA-BSI events was identified among 288 patients with malignancies. About 20% of cases were mixed infections (more than one isolate). Staphylococcus spp were the predominant isolated pathogen (24.7%), followed by Klebsiella spp (15.8%), Escherichia spp (13%), and Pseudomonas spp (9.3%). About half (51%) of cases died in the same year, and (64%) of the deaths occur within two weeks after the infection. According to the observations, no changes in the trends of epidemiology, causative pathogens, morbidity, and mortality rates in the last five years.

Keywords: epidemiology, haematological malignancies, hospital acquired bloodstream infections, solid malignancies

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Authors: Hawon Lee, Young-Pil Kim

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Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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Authors: Nidhal K. Azawi, John M. Gauch

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Colorectal cancer is one of the leading causes of cancer death in the US and the world, which is why millions of colonoscopy examinations are performed annually. Unfortunately, noise, specular highlights, and motion artifacts corrupt many images in a typical colonoscopy exam. The goal of our research is to produce automated techniques to detect and correct or remove these noninformative images from colonoscopy videos, so physicians can focus their attention on informative images. In this research, we first automatically extract features from images. Then we use machine learning and deep neural network to classify colonoscopy images as either informative or noninformative. Our results show that we achieve image classification accuracy between 92-98%. We also show how the removal of noninformative images together with image alignment can aid in the creation of image panoramas and other visualizations of colonoscopy images.

Keywords: colonoscopy classification, feature extraction, image alignment, machine learning

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Authors: Sean Hall

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Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

Procedia PDF Downloads 86

Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Chiara Cosentino, Carlo Pruneti, Carla Merisio, Domenico Sgromo

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Introduction – Psychoneuroimmunology as approach clearly showed how psychological features can influence health through specific physiological pathways linked to the stress reaction. This can be true also in cancer, in its latter conceptualization seen as a chronic disease. Therefore, it is still not clear how the psychological features can combine with a physiological specific path, for a better adjustment to cancer. The aim of this study is identifying how in Italian survivors, perceived social support, body image, coping and quality of life correlate with or influence Heart Rate Variability (HRV), the physiological parameter that can mirror a condition of chronic stress or a good relaxing capability. Method - The study had an exploratory transversal design. The final sample was made of 38 ovarian cancer survivors aged from 29 to 80 (M= 56,08; SD=12,76) following a program for Ovarian Cancer at the Oncological Clinic, University Hospital of Parma, Italy. Participants were asked to fill: Multidimensional Scale of Perceived Social Support (MSPSS); Derridford Appearance Scale-59 (DAS-59); Mental Adjustment to Cancer (MAC); Quality of Life Questionnaire (EORTC). For each participant was recorded Short-Term HRV (5 minutes) using emWavePro. Results– Data showed many interesting correlations within the psychological features. EORTC scores have a significant correlation with DAS-59 (r =-.327 p <.05), MSPSS (r =.411 p<.05), and MAC scores, in particular with the strategy Fatalism (r =.364 p<.05). A good social support improves HRV (F(1,33)= 4.27 p<.05). Perceiving themselves as effective in their environment, preserving a good role functioning (EORTC), positively affects HRV (F(1,33)=9.810 p<.001). Women admitting concerns towards body image seem prone to emotive disclosure, reducing emotional distress and improving HRV (β=.453); emotional avoidance worsens HRV (β=-.391). Discussion and conclusion - Results showed a strong relationship between body image and Quality of Life. These data suggest that higher concerns on body image, in particular, the negative self-concept linked to appearance, was linked to the worst functioning in everyday life. The relation between the negative self-concept and a reduction in emotional functioning is understandable in terms of possible distress deriving from the perception of body appearance. The relationship between a high perceived social support and a better functioning in everyday life was also confirmed. In this sample fatalism, was associated with a better physical, role and emotional functioning. In these women, the presence of a good support may activate the physiological Social Engagement System improving their HRV. Perceiving themselves effective in their environment, preserving a good role functioning, also positively affects HRV, probably following the same physiological pathway. A higher presence of concerns about appearance contributes to a higher HRV. Probably women admitting more body concerns are prone to a better emotive disclosure. This could reduce emotional distress improving HRV and global health. This study reached preliminary demonstration of an ‘Integrated Model of Defense’ in these cancer survivors. In these model, psychological features interact building a better quality of life and a condition of psychological well-being that is associated and influence HRV, then the physiological condition.

Keywords: cancer survivors, heart rate variability, ovarian cancer, psychophysiological adjustment

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Authors: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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Authors: Ali Kassem, Ehab Fawzy, Mahmoud Sef el-eslam, Fatma Salah- Eldeen, El zahraa Mohamed

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Introduction: The combination of interferon (INF) and ribavirin is the preferred treatment for chronic hepatitis C viral (HCV) infection. However, nonresponse to this therapy remains common and is associated with several factors such as HCV genotype and HCV viral load in addition to host factors such as sex, HLA type and cytokine polymorphisms. Aim of the work: The aim of this study was to determine predictors of response to (INF) therapy in chronic HCV infected patients treated with INF alpha and ribavirin combination therapy. Patients and Methods: The present study included 110 patients (62 males, 48 females) with chronic HCV infection. Their ages ranged from 20-59 years. Inclusion criteria were organized according to the protocol of the Egyptian National Committee for control of viral hepatitis. Patients included in this study were recruited to receive INF ribavirin combination therapy; 54 patients received pegylated NF α-2a (180 μg) and weight based ribavirin therapy (1000 mg if < 75 kg, 1200 mg if > 75 kg) for 48 weeks and 53 patients received pegylated INF α-2b (1.5 ug/kg/week) and weight based ribavirin therapy (800 mg if < 65 kg, 1000 mg if 65-75 kg and 1200 mg if > 75kg). One hundred and seven liver biopsies were included in the study and submitted to histopathological examination. Hematoxylin and eosin (H&E) stained sections were done to assess both the grade and the stage of chronic viral hepatitis, in addition to the degree of steatosis. Modified hepatic activity index (HAI) grading, modified Ishak staging and Metavir grading and staging systems were used. Laboratory follow up including: HCV PCR at the 12th week to assess the early virologic response (EVR) and at the 24th week were done. At the end of the course: HCV PCR was done at the end of the course and tested 6 months later to document end virologic response (ETR) and sustained virologic response (SVR) respectively. Results One hundred seven patients; 62 males (57.9 %) and 45 females (42.1%) completed the course and included in this study. The age of patients ranged from 20-59 years with a mean of 40.39±10.03 years. Six months after the end of treatment patients were categorized into two groups: Group (1): patients who achieved sustained virological response (SVR). Group (2): patients who didn't achieve sustained virological response (non SVR) including non-responders, breakthrough and relapsers. In our study, 58 (54.2%) patients showed SVR, 18 (16.8%) patients were non-responders, 15 (14%) patients showed break-through and 16 (15 %) patients were relapsers. Univariate binary regression analysis of the possible risk factors of non SVR showed that the significant factors were higher age, higher fasting insulin level, higher Metavir stage and higher grade of hepatic steatosis. Multivariate binary regression analysis showed that the only independent risk factor for non SVR was high fasting insulin level. Conclusion: Younger age, lower Metavir stage, lower steatosis grade and lower fasting insulin level are good predictors of SVR and could be used in predicting the treatment response of pegylated interferon/ribavirin therapy.

Keywords: chronic HCV infection, interferon ribavirin combination therapy, predictors to antiviral therapy, treatment response

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Authors: Muhammad G. Almatar, Mohammad A. Alnasrallah

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This research focuses on the study of three main issues: 1) The temporal analysis of leukemia for a period of six years (2006-2012), 2) spatial analysis by investigating this phenomenon in the Kuwaiti society spatially in the residential areas within the six governorates, 3) the use of Geographic Information System technology in investigating the hypothesis of the research and its variables using the linear regression, to show the pattern of linear relationship. The study depends on utilizing the map to understand the distribution of blood cancer in Kuwait. Several geodatabases were created for the number of patients and air pollution. Spatial interpolation models were used to generate layers of air pollution in the study area. These geodatabases were tested over the past six years to reach the conclusion: Is there a relationship with significant significance between the two main variables of the study: blood cancer and air pollution? This study is the first to our best knowledge. As far as the researchers know, the distribution of this disease has not been studied geographically at the level of regions in Kuwait within six years and in specific areas as described above. This study investigates the concentration of this type of disease. The study found that there is no relationship of significant value between the two variables studied, and this may be due to the nature of the disease, which are often hereditary. On the other hand, this study has reached a number of suggestions and recommendations that may be useful to decision-makers and interested in the study of leukemia in Kuwait by focusing on the study of genetic diseases, which may be a cause of leukemia rather than air pollution.

Keywords: Kuwait, GIS, cancer, geography

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Selim M. Khan, Aaron A. Goodarzi, Joshua M. Taron, Tryggve Rönnqvist

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Indoor air quality, a prime determinant of health, is strongly influenced by the presence of hazardous radon gas within the built environment. As a health issue, dangerously high indoor radon arose within the 20th century to become the 2nd leading cause of lung cancer. While the 21st century building metrics and human behaviors have captured, contained, and concentrated radon to yet higher and more hazardous levels, the issue is rapidly worsening in Canada. It is established that Canadians in the Prairies are the 2nd highest radon-exposed population in the world, with 1 in 6 residences experiencing 0.2-6.5 millisieverts (mSv) radiation per week, whereas the Canadian Nuclear Safety Commission sets maximum 5-year occupational limits for atomic workplace exposure at only 20 mSv. This situation is also deteriorating over time within newer housing stocks containing higher levels of radon. Deep machine learning (LSTM) algorithms were applied to analyze multiple quantitative and qualitative features, determine the most important contributory factors, and predicted radon levels in the known past (1990-2020) and projected future (2021-2050). The findings showed gradual downwards patterns in Sweden, whereas it would continue to go from high to higher levels in Canada over time. The contributory factors found to be the basement porosity, roof insulation depthness, R-factor, and air dynamics of the indoor environment related to human window opening behaviour. Building codes must consider including these factors to ensure adequate indoor ventilation and healthy living that can prevent lung cancer in non-smokers.

Keywords: radon, building metrics, deep learning, LSTM prediction model, lung cancer, canada, sweden

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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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Authors: Huang Wei-Yi

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Objective: This article explores the intensive care nursing experience of a lung cancer patient with pulmonary embolism who was placed on ECMO. Following a sudden change in the patient’s condition and a consensus reached during a family meeting, the decision was made to withdraw life-sustaining equipment and collaborate with the palliative care team. Methods: The nursing period was from October 20 to October 27, 2023. The author monitored physiological data, observed, provided direct care, conducted interviews, performed physical assessments, and reviewed medical records. Together with the critical care team and bypass personnel, a comprehensive assessment was conducted using Gordon's Eleven Functional Health Patterns to identify the patient’s health issues, which included pain related to lung cancer and invasive devices, fear of death due to sudden deterioration, and altered tissue perfusion related to hemodynamic instability. Results: The patient was admitted with fever, back pain, and painful urination. During hospitalization, the patient experienced sudden discomfort followed by cardiac arrest, requiring multiple CPR attempts and ECMO placement. A subsequent CT angiogram revealed a pulmonary embolism. The patient's condition was further complicated by severe pain due to compression fractures, and a diagnosis of terminal lung cancer was unexpectedly confirmed, leading to emotional distress and uncertainty about future treatment. Throughout the critical care process, ECMO was removed on October 24, stabilizing the patient’s body temperature between 36.5-37°C and maintaining a mean arterial pressure of 60-80 mmHg. Pain management, including Morphine 8mg in 0.9% N/S 100ml IV drip q6h PRN and Ultracet 37.5 mg/325 mg 1# PO q6h, kept the pain level below 3. The patient was transferred to the ward on October 27 and discharged home on October 30. Conclusion: During the care period, collaboration with the medical team and palliative care professionals was crucial. Adjustments to pain medication, symptom management, and lung cancer-targeted therapy improved the patient’s physical discomfort and pain levels. By applying the unique functions of nursing and the four principles of palliative care, positive encouragement was provided. Family members, along with social workers, clergy, psychologists, and nutritionists, participated in cross-disciplinary care, alleviating anxiety and fear. The consensus to withdraw ECMO and life-sustaining equipment enabled the patient and family to receive high-quality care and maintain autonomy in decision-making. A follow-up call on November 1 confirmed that the patient was emotionally stable, pain-free, and continuing with targeted lung cancer therapy.

Keywords: intensive care, lung cancer, pulmonary embolism, ECMO

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: M. L. Yeung

Abstract:

With the surge of divorce rate and male cancer onset/death rates, the phenomenon of divorced wives in the facing cancer death of their ex-husbands is not uncommon in Hong Kong. Yet, there is a dearth of study on the experiences of bereaved-divorced wives in the Hong Kong cultural context. This project fills the knowledge gap by conducting a qualitative study for having interviewed four bereaved ex-wives, who returned to ex-husbands’ end-of-life caregiving and eventually grieved for the ex-spousal’s death. From the perspectives of attachment theory and disenfranchised grief in the Hong Kong cultural context, a ‘double-loss’ experience is found in which interviewees suffer from the first loss of divorce and the second loss of ex-husbands’ death. Traumatic childhood experiences, attachment needs, role ambiguity, unresolved emotions and unrecognized grief are found significant in their lived experiences which alert the ‘double-loss’ is worthy of attention. Extending a family-centered end-of-life and bereavement care services to divorced couples is called for, in which validation on the attachment needs, ex-couple reconciliation, and acknowledgement on the disenfranchised grief are essential for social work practice on this group of clienteles specifically in Hong Kong cultural context.

Keywords: changing family, disenfranchised grief, divorce, ex-spousal death, marriage

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Authors: N. D'Amico, E. Grossi, B. Colombo, F. Rigiroli, M. Buscema, D. Fazzini, G. Cornalba, S. Papa

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Purpose: To characterize, through a radiomic approach, the nature of nodules considered non-specific by expert radiologists, recognized in magnetic resonance mammography (MRm) with T1-weighted (T1w) sequences with paramagnetic contrast. Material and Methods: 47 cases out of 1200 undergoing MRm, in which the MRm assessment gave uncertain classification (non-specific nodules), were admitted to the study. The clinical outcome of the non-specific nodules was later found through follow-up or further exams (biopsy), finding 35 benign and 12 malignant. All MR Images were acquired at 1.5T, a first basal T1w sequence and then four T1w acquisitions after the paramagnetic contrast injection. After a manual segmentation of the lesions, done by a radiologist, and the extraction of 150 radiomic features (30 features per 5 subsequent times) a machine learning (ML) approach was used. An evolutionary algorithm (TWIST system based on KNN algorithm) was used to subdivide the dataset into training and validation test and to select features yielding the maximal amount of information. After this pre-processing, different machine learning systems were applied to develop a predictive model based on a training-testing crossover procedure. 10 cases with a benign nodule (follow-up older than 5 years) and 18 with an evident malignant tumor (clear malignant histological exam) were added to the dataset in order to allow the ML system to better learn from data. Results: NaiveBayes algorithm working on 79 features selected by a TWIST system, resulted to be the best performing ML system with a sensitivity of 96% and a specificity of 78% and a global accuracy of 87% (average values of two training-testing procedures ab-ba). The results showed that in the subset of 47 non-specific nodules, the algorithm predicted the outcome of 45 nodules which an expert radiologist could not identify. Conclusion: In this pilot study we identified a radiomic approach allowing ML systems to perform well in the diagnosis of a non-specific nodule at MR mammography. This algorithm could be a great support for the early diagnosis of malignant breast tumor, in the event the radiologist is not able to identify the kind of lesion and reduces the necessity for long follow-up. Clinical Relevance: This machine learning algorithm could be essential to support the radiologist in early diagnosis of non-specific nodules, in order to avoid strenuous follow-up and painful biopsy for the patient.

Keywords: breast, machine learning, MRI, radiomics

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Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: Vaia N. Koukou, Niki D. Martini, George P. Fountos, Christos M. Michail, Athanasios Bakas, Ioannis S. Kandarakis, George C. Nikiforidis

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Various substitute materials of calcifications are used in phantom measurements and simulation studies in mammography. These include calcium carbonate, calcium oxalate, hydroxyapatite and aluminum. The aim of this study is to compare the contrast-to-noise ratio (CNR) values of the different calcification types using the dual energy method. The constructed calcification phantom consisted of three different calcification types and thicknesses: hydroxyapatite, calcite and calcium oxalate of 100, 200, 300 thicknesses. The breast tissue equivalent materials were polyethylene and polymethyl methacrylate slabs simulating adipose tissue and glandular tissue, respectively. The total thickness was 4.2 cm with 50% fixed glandularity. The low- (LE) and high-energy (HE) images were obtained from a tungsten anode using 40 kV filtered with 0.1 mm cadmium and 70 kV filtered with 1 mm copper, respectively. A high resolution complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) X-ray detector was used. The total mean glandular dose (MGD) and entrance surface dose (ESD) from the LE and HE images were constrained to typical levels (MGD=1.62 mGy and ESD=1.92 mGy). On average, the CNR of hydroxyapatite calcifications was 1.4 times that of calcite calcifications and 2.5 times that of calcium oxalate calcifications. The higher CNR values of hydroxyapatite are attributed to its attenuation properties compared to the other calcification materials, leading to higher contrast in the dual energy image. This work was supported by Grant Ε.040 from the Research Committee of the University of Patras (Programme K. Karatheodori).

Keywords: calcification materials, CNR, dual energy, X-rays

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Shaira L. Kee, Michael Aaron G. Sy, Myles Joshua T. Tan, Hezerul Abdul Karim, Nouar AlDahoul

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Skin diseases are considered the fourth most common disease, with melanoma and non-melanoma skin cancer as the most common type of cancer in Caucasians. The alarming increase in Skin Cancer cases shows an urgent need for further research to improve diagnostic methods, as early diagnosis can significantly improve the 5-year survival rate. Machine Learning algorithms for image pattern analysis in diagnosing skin lesions can dramatically increase the accuracy rate of detection and decrease possible human errors. Several studies have shown the diagnostic performance of computer algorithms outperformed dermatologists. However, existing methods still need improvements to reduce diagnostic errors and generate efficient and accurate results. Our paper proposes an ensemble method to classify dermoscopic images into benign and malignant skin lesions. The experiments were conducted using the International Skin Imaging Collaboration (ISIC) image samples. The dataset contains 3,297 dermoscopic images with benign and malignant categories. The results show improvement in performance with an accuracy of 88% and an F1 score of 87%, outperforming other existing models such as support vector machine (SVM), Residual network (ResNet50), EfficientNetB0, EfficientNetB4, and VGG16.

Keywords: deep learning - VGG16 - efficientNet - CNN – ensemble – dermoscopic images - melanoma

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Authors: Aleksandra Twarda, Dobrosława Krzemień, Grzegorz Dubin, Tad A. Holak

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Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.

Keywords: stabilin-2, Link domain, X-ray crystallography, NMR, hyaluronic acid, cancer

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