Search results for: molecular mechanisms of cancer

Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Vigen Arakelian

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The balancing of mechanisms is a well-known problem in the field of mechanical engineering because the variable dynamic loads cause vibrations, as well as noise, wear and fatigue of the machines. A mechanical system with unbalance shaking force and shaking moment transmits substantial vibration to the frame. Therefore, the objective of the balancing is to cancel or reduce the variable dynamic reactions transmitted to the frame. The resolution of this problem consists in the balancing of the shaking force and shaking moment. It can be fully or partially, by internal mass redistribution via adding counterweights or by modification of the mechanism's architecture via adding auxiliary structures. The balancing problems are of continue interest to researchers. Several laboratories around the world are very active in this area and new results are published regularly. However, despite its ancient history, mechanism balancing theory continues to be developed and new approaches and solutions are constantly being reported. Various surveys have been published that disclose particularities of balancing methods. The author believes that this is an appropriate moment to present a state of the art of the shaking force balancing studies completed by new research results. This paper presents an overview of methods devoted to the shaking force balancing of mechanisms, as well as the historical aspects of the origins and the evolution of the balancing theory of mechanisms.

Keywords: inertial forces, shaking forces, balancing, dynamics, mechanism design

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Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

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Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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Authors: Linda P. M. Pluymen, Mariska M. G. Leeflang, I. Stegeman, Henock G. Yebyo, Anne E. M. Brabers, Patrick M. Bossuyt, E. Dekker, Anke J. Woudstra, Mirjam P. Fransen

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Weighing the benefits and harms of colorectal cancer screening can be difficult for individuals. An existing online decision aid was expanded with a benefit-harm analysis to help people make an informed decision about participating in colorectal cancer screening. In a randomized controlled trial, we investigated whether those in the intervention group who used the decision aid with benefit-harm analysis were more certain about their decision than those in the control group who used the decision aid without benefit-harm analysis. Participants were 623 (39% of those invited) men and women aged 45 until 75 years old. Analyses were performed in those 386 participants (62%) who reported to have completed the entire decision aid. No statistically significant differences were observed between intervention and control group in decisional conflict score (mean difference 2.4, 95% CI -0.9, 5.6), clarity of values (mean difference 1.0, 95% CI -4.4, 6.6), deliberation score (mean difference 0.5, 95% CI -0.6, 1.7), anxiety score (mean difference 0.0, 95% CI -0.3, 0.3) and risk perception score (mean difference 0.1, -0.1, 0.3). Adding a benefit-harm analysis to an online decision aid did not improve informed decision making about participating in colorectal cancer screening.

Keywords: benefit-harm analysis, decision aid, informed decision making, personalized decision making

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Authors: R. Tudugala, B. M. A. I. Balasooriya, W. M. Ediri Arachchi, R. W. M. W. K. Rathnayake, T. D. Premaratna

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Brachytherapy involves placing a source of radiation near the cancer site which gives promising prognosis for cervical cancer treatments. The purpose of this study was to evaluate the effect of random variation of treated volumes in between fractions in the 2D image based fractionated high dose rate brachytherapy for cervical cancer at National Cancer Institute Maharagama, Sri Lanka. Dose plans were analyzed for 150 cervical cancer patients with orthogonal radiographs (2D) based brachytherapy. ICRU treated volumes was modeled by translating the applicators with the help of “Multisource HDR plus software”. The difference of treated volumes with respect to the applicator geometry was analyzed by using SPSS 18 software; to derived patient population based estimates of delivered treated volumes relative to ideally treated volumes. Packing was evaluated according to bladder dose, rectum dose and geometry of the dose distribution by three consultant radiation oncologist. The difference of treated volumes depends on types of the applicators, which was used in fractionated brachytherapy. The means of the “Difference of Treated Volume” (DTV) for “Evenly activated tandem (ET)” length” group was ((X_1)) -0.48 cm3 and ((X_2)) 11.85 cm3 for “Unevenly activated tandem length (UET) group. The range of the DTV for ET group was 35.80 cm3 whereas UET group 104.80 cm3. One sample T test was performed to compare the DTV with “Ideal treatment volume difference (0.00cm3)”. It is evident that P value was 0.732 for ET group and for UET it was 0.00 moreover independent two sample T test was performed to compare ET and UET groups and calculated P value was 0.005. Packing was evaluated under three categories 59.38% used “Convenient Packing Technique”, 33.33% used “Fairly Packing Technique” and 7.29% used “Not Convenient Packing” in their fractionated brachytherapy treatments. Random variation of treated volume in ET group is much lower than UET group and there is a significant difference (p<0.05) in between ET and UET groups which affects the dose distribution of the treatment. Furthermore, it can be concluded nearly 92.71% patient’s packing were used acceptable packing technique at NCIM, Sri Lanka.

Keywords: brachytherapy, cervical cancer, high dose rate, tandem, treated volumes

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Authors: A. Rajabpour, A. Hadizadeh Kheirkhah

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Heat transfer is of great importance to biological systems in order to function properly. In the present study, specific heat capacity as one of the most important heat transfer properties is calculated for a soluble in water Lysozyme protein. Using equilibrium molecular dynamics (MD) simulation, specific heat capacities of pure water, dry lysozyme, and lysozyme-water solution are calculated at 300K for different weight fractions. It is found that MD results are in good agreement with ideal binary mixing rule at small weight fractions. Results of all simulations have been validated with experimental data.

Keywords: specific heat capacity, molecular dynamics simulation, lysozyme protein, equilibrium

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Authors: Rahy Farooq, Maria Ahmad Khan, Ayesha Isani Majeed

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Objective: The main aim of this research is to assess the knowledge, attitude and practices of female nursing staff and nursing students regarding breast cancer, to provide a baseline for monitoring trends of breast cancer awareness in them. Background: Healthcare professionals are a direct source of information for the patients and the general public as a whole. It is, therefore, essential that the information they convey be accurate and helps in building additional awareness. However, clinical experience does not influence the knowledge, attitude and practices regarding breast cancer. Nurses, being the prime part of the healthcare professionals, play a significant role and hence, their awareness regarding this pressing issue is pertinent. Lack of awareness regarding common presenting symptoms or breast cancer risk factors translates to poor breast cancer screening practices and late diagnosis. Methodology: A cross-sectional study of 280 female nurses was conducted at a tertiary care hospital in Islamabad, Pakistan. A pre-tested structured questionnaire with additional variables like cultural barriers to seeking medical help was used. The scores for outcome variables including knowledge, attitude and practices were pre-defined. Data was analyzed using SPSSv23. Results: Of the 280 participants with a mean age of 28.99±9.98 years, 142 (50.7%) were married, and 138 (49.3%) were unmarried. Mean scores were computed to be 6.14±2.93 (out of 12), 0.30±0.7 (out of 3) and 9.53±1.92 (out of 16) for knowledge, attitude and practice respectively. Using independent sample T-test, a statistically significant correlation was found when means for the score of Attitude was compared with age. With a p-value of 0.018, 117 nurses of age more than 30 years, faced more practical, financial, emotional and service barriers as compared to 163 women younger than 30 years of age. Knowledge of age-related lifetime risks was also significantly poor more in single women; with a p-value of 0.006 for identification of correct age as a risk factor and a p-value of 0.005 for correct identification of risk for development of breast cancer in the lifetime of women. By application of Chi-square test, there was a significant correlation between marital status and cultural barriers to seeking medical help, showing that single women (58.7%) shy away from talking about breast cancer considering it a taboo (p-value 0.028) whereas, more married nurses (59.2%) were apprehensive that they might be considered at fault by the society, as compared to 40.8% of single nurses. (p-value 0.038). Conclusion: Owing to the scarcity of awareness among nurses, this study recognizes the need for delivering effective information to the female nurses regarding breast cancer. Educating patients is likely to be effective if the female nurses play their part and have correct attitudes towards breast cancer practices. A better understanding of the knowledge and practices regarding breast cancer among the nursing population will enable high-risk patients to be recognized early. Therefore, we recommend arrangement of special courses and seminars for all healthcare professionals including the nursing staff.

Keywords: breast cancer, cultural barriers, kap, nurses

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Authors: Liane J. Ioannou, Jonathan Serpell, Joanne Dean, Cino Bendinelli, Jenny Gough, Dean Lisewski, Julie Miller, Win Meyer-Rochow, Stan Sidhu, Duncan Topliss, David Walters, John Zalcberg, Susannah Ahern

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Background: The occurrence of thyroid cancer is increasing throughout the developed world, including Australia and New Zealand, and since the 1990s has become the fastest increasing malignancy. Following the success of a number of institutional databases that monitor outcomes after thyroid surgery, the Australian and New Zealand Endocrine Surgeons (ANZES) agreed to auspice the development of a bi-national thyroid cancer registry. Objectives: To establish a bi-national population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand. Patients and Methods: The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) captures clinical data for all patients, over the age of 18 years, diagnosed with thyroid cancer, confirmed by histopathology report, that have been diagnosed, assessed or treated at a contributing hospital. Data is collected by endocrine surgeons using a web-based interface, REDCap, primarily via direct data entry. Results: A multi-disciplinary Steering Committee was formed, and with operational support from Monash University the ANZTCR was established in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 30 sites expected to come on board across Australia and New Zealand in 2018. A modified-Delphi process was undertaken to determine the key quality indicators to be reported by the registry, and a minimum dataset was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery, and 30-day follow up. Conclusion: There are very few established thyroid cancer registries internationally, yet clinical quality registries have shown valuable outcomes and patient benefits in other cancers. The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand the current practice in the treatment of thyroid cancer and reasons for variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer-term outcome data particularly for patients with the poor prognostic disease will add significant further value to the registry.

Keywords: thyroid cancer, clinical registry, population health, quality improvement

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Authors: Olukayode Bamgbose, Feyisola Agboola, Adewale M. Taiwo, Olanrewaju Olujimi Oluwole Terebo, Azeez Soyingbe, Akeem Bamgbade

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The present study evaluated the contents and health risk assessment of metals determined in milk and milk product samples collected from the Abeokuta market. Forty-five milk and milk product (yoghurt) samples were digested and analysed for selected metals using Atomic Absorption Spectrophotometric method. Health risk assessment was evaluated for hazard quotient (HQ), hazard index (HI), and cancer risk (CR). Data were subjected to descriptive and inferential statistics. The concentrations of Zn, which ranged from 3.24±0.59 to 4.35±0.59 mg/kg, were the highest in the samples. Cr and Cd were measured below the detection limit of the analytical instrument, while the Pb level was higher than the Codex Alimentarius Commission value of 0.02 mg/kg, indicating unsafe for consumption. However, the HQ of Pb and other metals in milk and milk product samples was less than 1.0, thereby establishing no adverse health effects for Pb and other metals. The distribution pattern of metals in milk and milk product samples followed the decreasing order of Zn > Fe > Ni > Co > Cu > Mn > Pb > Cd/Cr. The CR levels of meals were also less than the permissible limit of 1.0 x 10-4, establishing no possible development of cancer. Keywords: adverse effects, cancer, metals, milk, milk product, the permissible limit.

Keywords: adverse effects, cancer, metals, milk, milk product, permissible limit

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Authors: Aileen F. Wang

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Mammography has been one of the most reliable methods for early detection and diagnosis of breast cancer. However, mammography misses about 17% and up to 30% of breast cancers due to the subtle and unstable appearances of breast cancer in their early stages. Recent computer-aided diagnosis (CADx) technology using Zernike moments has improved detection accuracy. However, it has several drawbacks: it uses manual segmentation, Zernike moments are not robust, and it still has a relatively high false negative rate (FNR)–17.6%. This project will focus on the development of a novel breast cancer detection algorithm to automatically segment the breast mass and further reduce FNR. The algorithm consists of automatic segmentation of a single breast mass using Point Region Growing Segmentation, reconstruction of the segmented breast mass using Pseudo-Zernike moments, and classification of the breast mass using the root mean square (RMS). A comparative study among the various algorithms on the segmentation and reconstruction of breast masses was performed on randomly selected mammographic images. The results demonstrated that the newly developed algorithm is the best in terms of accuracy and cost effectiveness. More importantly, the new classifier RMS has the lowest FNR–6%.

Keywords: computer aided diagnosis, mammography, point region growing segmentation, pseudo-zernike moments, root mean square

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Authors: Mushtaq Ahmad, Bashir Rahman, Taqweem-ul-Haq, Fazal Jalil, Aftab Ali Shah

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Single nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 G/C polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC-cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated, and the association between genotypes and the risk of BC was calculated by odds ratios (OR) and confidence intervals (95%). A significant difference in genotypic frequencies (χ2=63.10; p ≤ 0.0001) and allelic frequencies (OR=0.3955 (0.3132-0.4993); p ≤ 0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of breast cancer in the dominant (OR=0.2397 (0.1629-0.3526); p=0.0001; GG vs GC+CC) and recessive (OR=2.803 (1.865- 4.213); P ≤ 0.0001; CC vs GC+GG) inheritance models. In summary, miR-146a rs2910164 G/C is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm these findings.

Keywords: breast cancer, MIR146A, microRNA, SNP

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Authors: Emhemed Shaklawoon, Ibrahim Althomali

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We propose that we identify different defense mechanisms that were used before the introduction of the cloud and compare if their protection mechanisms are still valuable and to what degree. Note that in order to defend against vulnerability, we must know how this vulnerability is abused in an attack. Only then, we will be able to recognize if it is easier or harder to defend against cyber attacks.

Keywords: cloud computing, privacy, cyber attacks, defend the cloud

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Authors: Nouf Alharbi

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The electrospray deposition technique became an important method that enables fragile, nonvolatile molecules to be deposited in situ in high vacuum environments. Furthermore, it is considered one of the ways to close the gap between basic surface science and molecular engineering, which represents a gradual change in the range of scientist research. Also, this paper talked about one of the most important techniques that have been developed and aimed for helping to further develop and characterize the electrospray by providing data collected using an image charge detection instrument. Image charge detection mass spectrometry (CDMS) is used to measure speed and charge distributions of the molecular ions. As well as, some data has been included using SIMION simulation to simulate the energies and masses of the molecular ions through the system in order to refine the mass-selection process.

Keywords: charge, deposition, electrospray, image, ions, molecules, SIMION

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Authors: Jenny Jin

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Background: The therapeutic use of cannabis for cancer symptom control in Australia is gaining momentum, reflecting a broader global acceptance of its medicinal potential. Objective: This overview examines the historical context, current regulations, and clinical applications of cannabis in oncology within Australia. Methods: A historical analysis outlines the ancient and 19th-century medicinal uses of cannabis, followed by its prohibition in the early 20th century and subsequent resurgence in the late 20th century. The current legal framework under the therapeutic gods administration (TGA) is discussed. Results: Research indicates that cannabinoids, particularly THC and CBD, effectively alleviate pain, reduce chemotherapy-induced nausea and vomiting, stimulate appetite, and enhance overall quality of life for cancer patients. Despite these benefits, challenges such as dosing standardization, stigma, and access barriers persist. Conclusion: Continued clinical research, policy development, and educational initiatives are essential to optimize the use of cannabis in cancer care. A patient-centred approach, emphasizing interdisciplinary collaboration and informed decision-making, is crucial for improving therapeutic outcomes in this evolving field.

Keywords: historical context of cannabis, symptom control in oncology patients, therapeutic benefits, outcome and future

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Authors: Mahmoud Huleihil

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In this study, the performance of a thermodynamic gas cycle of magnetohydrodynamic (MHD) power generation is considered and presented in terms of power efficiency curves. The dissipation mechanisms considered include: fluid friction modeled by means of the isentropic efficiency of the compressor, heat transfer leakage directly from the hot reservoir to the cold heat reservoir, and constant velocity of the MHD generator. The study demonstrates that power and efficiency vanish at the extremes of both slow and fast operating conditions. These points are demonstrated on power efficiency curves and the locus of efficiency at maximum power and the locus of maximum efficiency. Qualitatively, the considered loss mechanisms have a similar effect on the efficiency at maximum power operation and on maximum efficiency operation, thus these efficiencies are reduced, even for small values of the loss mechanisms.

Keywords: magnetohydrodynamic generator, electrical efficiency, maximum power, maximum efficiency, heat engine

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Authors: Amina Aquil, Abdeljalil El Got

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Background: Sleep quality is one of the most important indicators related to the quality of life of patients suffering from cancer. Many factors could affect this quality of sleep and then be considered as associated predictors. Methods: The aim of this study was to assess the prevalence of sleep disorders and the associated factors with impaired sleep quality in Moroccan women with gynecological cancer. A cross-sectional study was carried out within the oncology department of the Ibn Rochd University Hospital, Casablanca, on Moroccan women who had undergone radical surgery for gynecological cancer (n=100). Translated and validated Arabic versions of the following international scales were used: Pittsburgh sleep quality index (PSQI), Hospital Anxiety and Depression Scale (HADS), Rosenberg's self-esteem scale (RSES), and Body image scale (BIS). Results: 78% of participants were considered poor sleepers. Most of the patients exhibited very poor subjective quality, low sleep latency, a short period of sleep, and a low rate of usual sleep efficiency. The vast majority of these patients were in poor shape during the day and did not use sleep medication. Waking up in the middle of the night or early in the morning and getting up to use the bathroom were the main reasons for poor sleep quality. PSQI scores were positively correlated with anxiety, depression, body image dissatisfaction, and lower self-esteem (p < 0.001). Conclusion: Sleep quality and its predictors require a systematic evaluation and adequate management to prevent sleep disturbances and mental distress as well as to improve the quality of life of these patients.

Keywords: body image, gynecological cancer, self esteem, sleep quality

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Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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Authors: Gerardo Arias, Richard Wall, Jamie Stevens

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Lucilia bufonivora Moniez, is an obligate parasite of toads and frogs widely distributed in Europe. Its sister taxon Lucilia silvarum Meigen behaves mainly as a carrion breeder in Europe, however it has been reported as a facultative parasite of amphibians. These two closely related species are morphologically almost identical, which has led to misidentification, and in fact, it has been suggested that the amphibian myiasis cases by L. silvarum reported in Europe should be attributed to L. bufonivora. Both species remain poorly studied and their taxonomic relationships are still unclear. The identification of the larval specimens involved in amphibian myiasis with molecular tools and phylogenetic analysis of these two closely related species may resolve this problem. In this work seventeen unidentified larval specimens extracted from toad myiasis cases of the UK, the Netherlands and Switzerland were obtained, their COX1 (mtDNA) and EF1-α (Nuclear DNA) gene regions were amplified and then sequenced. The 17 larval samples were identified with both molecular markers as L. bufonivora. Phylogenetic analysis was carried out with 10 other blowfly species, including L. silvarum samples from the UK and USA. Bayesian Inference trees of COX1 and a combined-gene dataset suggested that L. silvarum and L. bufonivora are separate sister species. However, the nuclear gene EF1-α does not appear to resolve their relationships, suggesting that the rates of evolution of the mtDNA are much faster than those of the nuclear DNA. This work provides the molecular evidence for successful identification of L. bufonivora and a molecular analysis of the populations of this obligate parasite from different locations across Europe. The relationships with L. silvarum are discussed.

Keywords: calliphoridae, molecular evolution, myiasis, obligate parasitism

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Authors: Kamila Duś-Szachniewicz, Kinga M. Walaszek, Paweł Skiba, Paweł Kołodziej, Piotr Ziółkowski

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Cell adhesion is of fundamental importance in the cell communication, signaling, and motility, and its dysfunction occurs prevalently during cancer progression. The knowledge of the molecular and cellular processes involved in abnormalities in cancer cells adhesion has greatly increased, and it has been focused mainly on cellular adhesion molecules (CAMs) and tumor microenvironment. Unfortunately, most of the data regarding CAMs expression relates to study on cells maintained in standard oxygen condition of 21%, while the emerging evidence suggests that culturing cells in ambient air is far from physiological. In fact, oxygen in human tissues ranges from 1 to 11%. The aim of this study was to compare the effects of physiological lymph node normoxia (5% O2), and hyperoxia (21% O2) on the expression of cellular adhesion molecules of primary diffuse large B-cell lymphoma cells (DLBCL) isolated from 10 lymphoma patients. Quantitative RT-PCR and immunohistochemistry were used to confirm the differential expression of several CAMs, including ICAM, CD83, CD81, CD44, depending on the level of oxygen. Our findings also suggest that DLBCL cells maintained at ambient O2 (21%) exhibit reduced growth rate and migration ability compared to the cells growing in normoxia conditions. Taking into account all the observations, we emphasize the need to identify the optimal human cell culture conditions mimicking the physiological aspects of tumor growth and differentiation.

Keywords: adhesion molecules, diffuse large B-cell lymphoma, physiological normoxia, quantitative RT-PCR

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Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

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Purpose: 18F Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a noninvasive imaging modality that can identify nodal metastases in women with primary breast cancer. The aim of this study was to compare the accuracy of FDG-PET with MRI and sonography scanning to determine axillary lymph node status in patients with breast cancer undergoing sentinel lymph node biopsy or axillary lymph node dissection. Patients and Methods: Between January and December 2012, ninety-nine patients with breast cancer and clinically negative axillary nodes were evaluated. All patients underwent FDG-PET, MRI, ultrasound followed by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Results: Using axillary lymph node assessment as the gold standard, the sensitivity and specificity of FDG-PET were 51.4% (95% CI, 41.3% to 65.6%) and 92.2% (95% CI, 82.7% to 97.4%) respectively. The sensitivity and specificity of MRI and ultrasound were 57.1% (95% CI, 39.4% to 73.7%), 67.2% (95% CI, 54.3% to 78.4%) and 42.86% (95% CI, 26.3% to 60.7%), 92.2% (95% CI, 82.7% to 97.4%). Stratification according to hormone receptor status showed an increase in specificity when negative (FDG-PET: 42.3% to 77.8%, MRI 50% to 77.8%, ultrasound 34.6% to 66.7%). Also, positive HER2 status was associated with an increase in specificity (FDG-PET: 42.9% to 85.7%, MRI 50% to 85.7%, ultrasound 35.7% to 71.4%). Conclusions: The sensitivity and specificity of FDG-PET compared with MRI and ultrasound was high. However, FDG-PET is not sufficiently accurate to appropriately identify lymph node metastases. This study suggests that FDG-PET scanning cannot replace histologic staging in early-stage breast cancer, but might have a role in evaluating axillary lymph node status in hormone receptor negative or HER-2 overexpressing subtypes.

Keywords: axillary lymph node metastasis, FDG-PET, MRI, ultrasound

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Authors: Jyoti Srivastava, Sandhya S. Kaushik, Mallika Tewari, Hari S. Shukla

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Little information is available about the development of psychological well being over time among women who have been undergoing treatment for breast cancer. The aim of this study was to identify the trajectories of depression anxiety and stress among women with early-stage breast cancer. Of the 48 Indian women with newly diagnosed early-stage breast cancer recruited from surgical oncology unit, 39 completed an interview and were assessed for depression anxiety and stress (Depression Anxiety Stress Scale-DASS 21) before their first course of chemotherapy (baseline) and follow up interviews at 3, 6 and 9 months thereafter. Growth mixture modeling was used to identify distinct trajectories of Depression Anxiety and Stress symptoms. Logistic Regression analysis was used to evaluate the characteristics of women in distinct groups. Most women showed mild to moderate level of depression and anxiety (68%) while normal to mild level of stress (71%). But one in 11 women was chronically anxious (9%) and depressed (9%). Young age, having a partner, shorter education and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong nine months after diagnosis. By looking beyond the mean, it was found that several socio-demographic and treatment factors characterized the women whose depression, anxiety and stress level remained severe even nine months after diagnosis. The results suggest that support provided to cancer patients should have a special focus on a relatively small group of patient most in need.

Keywords: psychological well being, growth mixture modeling, logistic regression analysis, socio-demographic factors

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Authors: Jiahui Song

Abstract:

The use of high-intensity, nanosecond electric pulses has been a recent development in biomedical. High-intensity (∼100 kV/cm), nanosecond duration-pulsed electric fields have been shown to induce cellular electroporation. This will lead to an increase in transmembrane conductivity and diffusive permeability. These effects will also alter the electrical potential across the membrane. The applications include electrically triggered intracellular calcium release, shrinkage of tumors, and temporary blockage of the action potential in nerves. In this research, the dynamics of pore formation with the presence of an externally applied electric field is studied on the basis of molecular dynamics (MD) simulations using the GROMACS package. MD simulations show pore formation occurs for a pulse with the amplitude of 0.5V/nm at 1ns at temperature 316°K. Also increasing temperatures facilitate pore formation. When the temperature is increased to 323°K, pore forms at 0.75ns with the pulse amplitude of 0.5V/nm. For statistical significance, a total of eight MD simulations are carried out with different starting molecular velocities for each simulation. Also, actual experimental observations are compared against MD simulation results.

Keywords: molecular dynamics, high-intensity, nanosecond, electroporation

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Authors: Mahya Naghipoor

Abstract:

Purpose: Non-small cell lung cancer (NSCLC) is the most common lung cancer type. Epidermal growth factor receptor (EGFR) mutation is the main reason which causes NSCLC. Computed tomography (CT) is used for diagnosis and prognosis of lung cancers because of low price and little invasion. Semantic analyses of qualitative CT features are based on visual evaluation by radiologist. However, the naked eye ability may not assess all image features. On the other hand, radiomics provides the opportunity of quantitative analyses for CT images features. The aim of this review study was comparing accuracy of semantic and radiomics features in prognosis of EGFR mutation in NSCLC. Methods: For this purpose, the keywords including: non-small cell lung cancer, epidermal growth factor receptor mutation, semantic, radiomics, feature, receiver operating characteristics curve (ROC) and area under curve (AUC) were searched in PubMed and Google Scholar. Totally 29 papers were reviewed and the AUC of ROC analyses for semantic and radiomics features were compared. Results: The results showed that the reported AUC amounts for semantic features (ground glass opacity, shape, margins, lesion density and presence or absence of air bronchogram, emphysema and pleural effusion) were %41-%79. For radiomics features (kurtosis, skewness, entropy, texture, standard deviation (SD) and wavelet) the AUC values were found %50-%86. Conclusions: In conclusion, the accuracy of radiomics analysis is a little higher than semantic in prognosis of EGFR mutation in NSCLC.

Keywords: lung cancer, radiomics, computer tomography, mutation

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Emma K. Sales, Nilda G. Butardo

Abstract:

The project was undertaken to determine the effects of modified tissue culture protocols e.g. age of culture and hormone levels (2,4-D) in generating somaclonal variation. Moreover, the utility of molecular markers (SSR and MSAP) in sorting off types/somaclones were investigated. Results show that somaclonal variation is in effect due to prolonged subculture and high 2,4-D concentration. The resultant variation was observed to be due to high level of methylation events specifically cytosine methylation either at the internal or external cytosine and was identified by methylation sensitive amplification polymorphism (MSAP). Simple sequence repeats (SSR) on the other hand, was able to associate a marker to a trait of interest. These therefore, show that molecular markers can be an important tool in sorting out variation/mutants at an early stage.

Keywords: methylation, MSAP, somaclones, SSR, subculture, 2, 4-D

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Authors: Maxime Moreau, Silvère Baron, Jean-Marc Lobaccaro, Karine Charlet, Sébastien Menecier, Frédéric Perisse

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Cold Atmospheric Plasma (CAP) is an ionized gas generated at atmospheric pressure with the temperature of heavy particles (molecules, ions, atoms) close to the room temperature. Recent studies have shown that both in-vitro and in-vivo plasma exposition to many cancer cell lines are efficient to induce the apoptotic way of cell death. In some other works, normal cell lines seem to be less impacted by plasma than cancer cell lines. This is called selectivity of plasma. It is highly likely that the generated RNOS (Reactive Nitrogen Oxygen Species) in the plasma jet, but also in the medium, play a key-role in this selectivity. In this study, two CAP devices will be compared to electrical power, chemical species composition and their efficiency to kill cancer cells. A particular focus on the action of hydrogen peroxide will be made. The experiments will take place as described next for both devices: electrical and spectroscopic characterization for different voltages, plasma treatment of normal and cancer cells to compare the CAP efficiency between cell lines and to show that death is induced by an oxidative stress. To enlighten the importance of hydrogen peroxide, an inhibitor of H2O2 will be added in cell culture medium before treatment and a comparison will be made between the results of cell viability in this case and those from a simple plasma exposition. Besides, H2O2 production will be measured by only treating medium with plasma. Cell lines will also be exposed to different concentrations of hydrogen peroxide in order to characterize the cytotoxic threshold for cells and to make a comparison with the quantity of H2O2 produced by CAP devices. Finally, the activity of catalase for different cell lines will be quantified. This enzyme is an important antioxidant agent against hydrogen peroxide. A correlation between cells response to plasma exposition and this activity could be a strong argument in favor of the predominant role of H2O2 to explain the selectivity of plasma cancer treatment by cold atmospheric plasma.

Keywords: cold atmospheric plasma, hydrogen peroxide, prostate cancer, selectivity

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Jean Paul M. Milambo

Abstract:

Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

Abstract:

Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

Abstract:

The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

Procedia PDF Downloads 580