Search results for: cancer research

Authors: Abebe Mulugojam Negash, Yongbin Yu, Ekong Favour, Bekalu Nigus Dawit, Molla Woretaw Teshome, Aynalem Birtukan Yirga

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Breast cancer remains a significant health concern, necessitating advancements in diagnostic methodologies. Addressing this, our paper confronts the notable challenges in breast cancer classification, particularly the imbalance in datasets and the constraints in the accuracy and interpretability of prevailing deep learning approaches. We proposed an attention-based residual neural network (ResNet), which effectively combines the robust features of ResNet with an advanced attention mechanism. Enhanced through strategic data augmentation and positive weight adjustments, this approach specifically targets the issue of data imbalance. The proposed model is tested on the BreakHis dataset and achieved accuracies of 99.00%, 99.04%, 98.67%, and 98.08% in different magnifications (40X, 100X, 200X, and 400X), respectively. We evaluated the performance by using different evaluation metrics such as precision, recall, and F1-Score and made comparisons with other state-of-the-art methods. Our experiments demonstrate that the proposed model outperforms existing approaches, achieving higher accuracy in breast cancer classification.

Keywords: residual neural network, attention mechanism, positive weight, data augmentation

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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

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

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Authors: Jitpisute Chunthorng-Orn, Thana Juckmeta, Onmanee Prajuabjinda, Arunporn Itharat

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Inflammation and oxidative stress work together to produce symptoms in cancer patients. The whole part of it is used as a preparation to treat cancer patients in Khampramong temple which has been a place of treatment and palliative care for cancer patients since 2005. Thus, the objective of this study was to investigate anti-inflammatory and antioxidant activities of Heliotropium indicum extracts. Dried plant materials were extracted in a similar manner to those practiced by the Khampramong Temple i.e. maceration in 95% ethanol and boiling in water. For anti-inflammation activity, both extracts were tested for suppression of nitric oxide (NO) production in LPS-induced RAW 264.7 cells. They were also tested for antioxidant activity by DPPH radical scavenging assay. This study found that the ethanolic extract of Heliotropium indicum exhibited higher inhibitory activity of NO release than Indomethacin as a positive control (IC50 value of 24.17±2.12 and 34.67±6.23 μg/mL, respectively). For DPPH radical scavenging assay, the ethanolic extract also exhibited antioxidant activity but less than BHT as a antioxidant compound (EC50 values = 28.91±4.26 and 13.08±0.29 μg/mL, respectively). In contrast, its water extract had no inhibitory activity on NO release (IC50 > 100 μg/mL) and no inhibitory activity on DPPH radicals (EC50 values > 100 μg/mL). The results showed correlation between anti-inflammation and antioxidant activity and these results also support using this plant to treat cancer patients.

Keywords: Heliotropium indicum, RAW 264.7, DPPH, Khampramong Temple

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Authors: Nassim Salmi

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Postoperative mobilization is an important part of fundamental care. Increased mobilization has a positive effect on recovery, but immobilization is still a challenge in postoperative care. Aims: To report how the establishment of a national nursing database was used to measure postoperative mobilization in patients undergoing surgery for ovarian cancer. Mobilization was defined as at least 3 hours out of bed on postoperative day 1, with the goal set at achieving this in 60% of patients. Clinical nurses on 4400 patients with ovarian cancer performed data entry. Findings: 46.7% of patients met the goal for mobilization on the first postoperative day, but variations in duration and type of mobilization were observed. Of those mobilized, 51.8% had been walking in the hallway. A national nursing database creates opportunities to optimize fundamental care. By comparing nursing data with oncological, surgical, and pathology data, it became possible to study mobilization in relation to cancer stage, comorbidity, treatment, and extent of surgery.

Keywords: postoperative care, gynecology, nursing documentation, database

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

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

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

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Authors: A. Dean, M. Pitcher, L. Storer, K. Shanahan, I. Rio, B. Mann

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Purpose: Breast cancer survivors are at risk of specific physical and psycho-social issues, such as arm swelling, fatigue, and depression. Firstly, we investigate symptoms reported by Australia breast cancer survivors upon completion of definitive treatment. Secondly, we evaluate the appropriateness and effectiveness of a multi-centre pilot program nurse-led clinic to identify these issues and make timely referrals to available services. Methods: Patients post-definitive treatment (excluding ongoing hormonal therapy) for early breast cancer or ductal carcinoma in situ were invited to participate. An hour long appointment with a breast care nurse (BCN) was scheduled. In preparation, patients completed validated quality-of-life surveys (FACT-B, Menopause Rating Scale, Distress Thermometer). During the appointment, issues identified in the surveys were addressed and referrals to appropriate services arranged. Results: 183 of 274 (67%) eligible patients attended a nurse-led clinic. Mean age 56.8 years (range 29-87 years), 181/183 women, 105/183 post-menopausal. 96 (55%) participants reported significant level of distress; 31 (18%) participants reported extreme distress or depression. Distress stemmed from a lack of energy (56/175); poor quality of sleep (50/176); inability to work or participate in household activities (35/172) and problems with sex life (28/89). 166 referrals were offered; 94% of patients accepted the referrals. 65% responded to a follow-up survey: the majority of women either strongly agreed or agreed that the BCN was overwhelmingly supportive, helpful in making referrals, and compassionate towards them. 39% reported making lifestyle changes as a result of the BCN. Conclusion: Breast cancer survivors experience a unique set of challenges, including low mood, difficulty sleeping, problems with sex life and fear of disease recurrence. The nurse-led clinic model is an appropriate and effective method to ensure physical and psycho-social issues are identified and managed in a timely manner. This model empowers breast cancer survivors with information about their diagnosis and available services.

Keywords: early breast cancer, survivorship, breast care nursing, oncology nursing and cancer care

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Khadija Al-Hosni, Moon Fai Chan, Mohammed Al-Azri

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Background: Several studies suggest that most school-age adolescents are poorly informed on cancer warning signs and risk factors. Providing adolescents with sufficient knowledge would increase their awareness in adulthood and improve seeking behaviors later. Significant: The results will provide a clear vision in assisting key decision-makers in formulating policies on the students' awareness programs towards cancer. So, the likelihood of avoiding cancer in the future will be increased or even promote early diagnosis. Objectives: to evaluate the effectiveness of an education program designed to increase awareness of cancer signs and symptoms risk factors, improve the behavior of seeking help among school students in Oman, and address the barriers to obtaining medical help. Methods: A randomized controlled trial with two groups was conducted in Oman. A total of 1716 students (n=886/control, n= 830/education), aged 15-17 years, at 10th and 11th grade from 12 governmental schools 3 in governorates from 20-February-2022 to 12-May-2022. Basic demographic data were collected, and the Cancer Awareness Measure (CAM) was used as the primary outcome. Data were collected at baseline (T0) and 4 weeks after (T1). The intervention group received an education program about cancer's cause and its signs and symptoms. In contrast, the control group did not receive any education related to this issue during the study period. Non-parametric tests were used to compare the outcomes between groups. Results: At T0, the lamp was the most recognized cancer warning sign in the control (55.0%) and intervention (55.2%) groups. However, there were no significant changes at T1 for all signs in the control group. In contrast, all sign outcomes were improved significantly (p<0.001) in the intervention group, and the highest response was unexplained pain (93.3%). Smoking was the most recognized risk factor in both groups: (82.8% for control; 84.1% for intervention) at T0. However, there was no significant change in T1 for the control group, but there was for the intervention group (p<0.001), the highest identification was smoking cigarettes (96.5%). Too scared was the largest barrier to seeking medical help by students in the control group at T0 (63.0%) and T1 (62.8%). However, there were no significant changes in all barriers in this group. Otherwise, being too embarrassed (60.2%) was the largest barrier to seeking medical help for students in the intervention group at T0 and too scared (58.6%) at T1. Although there were reductions in all barriers, significant differences were found in six of ten only (p<0.001). Conclusion: The intervention was effective in improving students' awareness of cancer symptoms, warning signs (p<0.001), and risk factors (p<0.001 reduced the most addressed barriers to seeking medical help (p<0.001) in comparison to the control group. The Ministry of Education in Oman could integrate awareness of cancer within the curriculum, and more interventions are needed on the sociological part to overcome the barriers that interfere with seeking medical help.

Keywords: adolescents, awareness, cancer, education, intervention, student

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Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

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Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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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: 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: 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: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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

Abstract:

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: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

Abstract:

Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Aileen F. Wang

Abstract:

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

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

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

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Ayyaz Hussain, Tariq Sadad

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Breast cancer (BC) is one of the widespread ailments among females globally. The early prognosis of BC can decrease the mortality rate. Exact findings of benign tumors can avoid unnecessary biopsies and further treatments of patients under investigation. However, due to variations in images, it is a tough job to isolate cancerous cases from normal and benign ones. The machine learning technique is widely employed in the classification of BC pattern and prognosis. In this research, a deep convolution neural network (DCNN) called AlexNet architecture is employed to get more discriminative features from breast tissues. To achieve higher accuracy, K-nearest neighbor (KNN) classifiers are employed as a substitute for the softmax layer in deep learning. The proposed model is tested on a widely used breast image database called MIAS dataset for experimental purposes and achieved 99% accuracy.

Keywords: breast cancer, DCNN, KNN, mammography

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Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra

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The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.

Keywords: biomarkers, oral cancer, organic solvents, shoe industries

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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: Amina Aquil, Abdeljalil El Got

Abstract:

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: Osama Shakeel

Abstract:

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

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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: 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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