Search results for: risk of cancer

Authors: Xiaoping Su, Gabriel G. Malouf

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Introduction: Breast cancer is a heterogeneous disease that can be classified in 4 subgroups using transcriptional profiling. The role of lncRNA expression in human breast cancer biology, prognosis, and molecular classification remains unknown. Methods and results: Using an integrative comprehensive analysis of lncRNA, mRNA and DNA methylation in 900 breast cancer patients from The Cancer Genome Atlas (TCGA) project, we unraveled the molecular portraits of 1,700 expressed lncRNA. Some of those lncRNAs (i.e, HOTAIR) are previously reported and others are novel (i.e, HOTAIRM1, MAPT-AS1). The lncRNA classification correlated well with the PAM50 classification for basal-like, Her-2 enriched and luminal B subgroups, in contrast to the luminal A subgroup which behaved differently. Importantly, estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Gene set enrichment analysis for cis- and trans-acting lncRNA showed enrichment for breast cancer signatures driven by breast cancer master regulators. Almost two third of those lncRNA were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that lncRNA expression may result in increased activity of neighboring genes. Differential analysis of gene expression profiling data showed that lncRNA HOTAIRM1 was significantly down-regulated in basal-like subtype, and DNA methylation profiling data showed that lncRNA HOTAIRM1 was highly methylated in basal-like subtype. Thus, our integrative analysis of gene expression and DNA methylation strongly suggested that lncRNA HOTAIRM1 should be a tumor suppressor in basal-like subtype. Conclusion and significance: Our study depicts the first lncRNA molecular portrait of breast cancer and shows that lncRNA HOTAIRM1 might be a novel tumor suppressor.

Keywords: lncRNA profiling, breast cancer, HOTAIRM1, tumor suppressor

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Authors: Sylwia Frydrych, Jörg Prokop, Michał Buszko

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This study investigates the complex relationship between corporate ESG (Environmental, Social, Governance) performance and stock price risk within the European market context. By analyzing a dataset of 435 companies across 19 European countries, the research assesses the impact of both combined ESG performance and its individual components on various risk measures, including volatility, idiosyncratic risk, systematic risk, and downside risk. The findings reveal that while overall ESG scores do not significantly influence stock price risk, disaggregating the ESG components uncovers significant relationships. Governance practices are shown to consistently reduce market risk, positioning them as critical in risk management. However, environmental engagement tends to increase risk, particularly in times of regulatory shifts like those introduced in the EU post-2018. This research provides valuable insights for investors and corporate managers on the nuanced roles of ESG factors in financial risk, emphasizing the need for careful consideration of each ESG pillar in decision-making processes.

Keywords: ESG performance, ESG factors, ESG pillars, ESG scores

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Authors: Neda Menbari, Ramin Mehdiabadi

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Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Omer Ibrahim Abdallh Omer

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Cancer patients often face complex medication regimens, leading to challenges in treatment adherence and clinical outcomes. Pharmacist-led medication therapy management (MTM) has emerged as a potential solution to optimize medication use and improve patient outcomes in oncology settings. In this prospective intervention study, we aimed to evaluate the impact of pharmacist-led MTM on treatment adherence and clinical outcomes among cancer patients. Participants were randomized to receive either pharmacist-led MTM or standard care, with assessments conducted at baseline and follow-up visits. Pharmacist interventions included medication reconciliation, adherence counseling, and personalized care plans. Our findings reveal that pharmacist-led MTM significantly improved medication adherence rates and clinical outcomes compared to standard care. Patients receiving pharmacist interventions reported higher satisfaction levels and perceived value in pharmacist involvement in their cancer care. These results underscore the critical role of pharmacists in optimizing medication therapy and enhancing patient-centered care in oncology settings. Integration of pharmacist-led MTM into routine cancer care pathways holds promise for improving treatment outcomes and quality of life for cancer patients.

Keywords: cancer, medications adherence, medication therapy management, pharmacist

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Authors: Rizwan Arshad, Alessio Panza, Nimra Inayat, Syeda Mariam Batool Kazmi, Shawana Azmat

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The rapidly expanding use of immunotherapy for a wide range of cancers from late to early stages has, predictably, been accompanied by evidence of inequities in access to these highly effective but costly treatments. In this survey-based case study, we aimed to develop a One-window services model (OWSM) based on Anderson’s behavioral model to enhance competence in accessing cancer medications, particularly immunotherapies, through the analysis of 20 patient surveys conducted in the Armed forces bone marrow transplant center of the district, Rawalpindi from November to December 2022. The purposive sampling technique was used. Cronbach’s alpha coefficient was found to be 0.71. It was analyzed using SPSS version 26 with descriptive analysis, and results showed that the majority of the cancer patients were non-competent to access their prescribed cancer immunotherapy because of individual-level, socioeconomic, and organizational barriers.

Keywords: cancer immunotherapy, one-window services model, accessibility, competence

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Authors: Carlos Huertas, Reyes Juarez-Ramirez

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Public health is one of the most critical issues today; therefore, there is great interest to improve technologies in the area of diseases detection. With machine learning and feature selection, it has been possible to aid the diagnosis of several diseases such as cancer. In this work, we present an extension to the Heat Map Based Feature Selection algorithm, this modification allows automatic threshold parameter selection that helps to improve the generalization performance of high dimensional data such as mass spectrometry. We have performed a comparison analysis using multiple cancer datasets and compare against the well known Recursive Feature Elimination algorithm and our original proposal, the results show improved classification performance that is very competitive against current techniques.

Keywords: biomarker discovery, cancer, feature selection, mass spectrometry

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Authors: Ahmet Parlak, Celalettin Bilgen

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In order to create an effective early warning system, Identification of the risks, preparation and carrying out risk modeling of risk scenarios, taking into account the shortcomings of the old disaster scenarios should be used to improve the system. In the light of this, the importance of risk modeling in creating an effective early warning system is understood. In the scope of TAFRISK project risk modeling trend analysis report on risk modeling developed and a demonstration was conducted for Risk Modeling for flood and mass movements. For risk modeling R&D, studies have been conducted to determine the information, and source of the information, to be gathered, to develop algorithms and to adapt the current algorithms to Turkey’s conditions for determining the risk score in the high disaster risk areas. For each type of the disaster; Disaster Deficit Index (DDI), Local Disaster Index (LDI), Prevalent Vulnerability Index (PVI), Risk Management Index (RMI) have been developed as disaster indices taking danger, sensitivity, fragility, and vulnerability, the physical and economic damage into account in the appropriate scale of the respective type.

Keywords: disaster, hazard, risk modeling, sensor

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Authors: Robin L. Rohrer

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Introduction: Pre-natal or early childhood exposure to the medical radiation used in diagnosis or treatment is an identified risk for childhood cancers but can be difficult to document. The author developed a family questionnaire/interview form to identify possible exposures. Aims: This retrospective study examines pre-natal and early childhood medical radiation exposure in a cohort of children diagnosed with a solid tumor including brain tumors from 1985-2015 at the Children’s Hospital of Pittsburgh (CHP). The hospital is a tri-state regional referral center which treats about 150-180 new cases of cancer in children per year. About 70% are diagnosed with a solid tumor. Methods: Each consented family so far (approximately 50% of the cohort) has been interviewed in person or by the phone call. Medical staff and psycho- social staff referred patient families for the interview with the author. Results: Among the families interviewed to date at least one medical radiation exposure has been identified (pre-conception, pre-natal or early childhood) in over 70% of diagnosed children. These exposures have included pre-conception sinus or chest CT or X-ray in either parent, sinus CT or X-ray in the mother or diagnostic radiation of chest or abdomen in children. Conclusions: Exposures to medical radiation for a child later diagnosed with cancer may occur at several critical junctures. These exposures may well contribute to a ‘perfect storm’ in the still elusive causes of childhood cancer. The author plans to expand the study from 1975 to present to hopefully further document these junctures.

Keywords: pediatric, solid tumors, medical radiation, cancer

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Authors: Tzu-Ting Hu, Jung-Der Wang, Ming-Yeng Lin, Jin-Luh Chen, Perng-Jy Tsai

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The vinyl chloride monomer (VCM) has been classified as group 1 (human) carcinogen by the IARC. Workers exposed to VCM are known associated with the development of the liver cancer and hence might cause economical and health losses. Particularly, for those work for the petrochemical industry have been seriously concerned in the environmental and occupational health field. Considering assessing workers’ health risks and their resultant economical and health losses requires the establishment of long-term VCM exposure data for any similar exposure group (SEG) of interest, the development of suitable technologies has become an urgent and important issue. In the present study, VCM exposures for petrochemical industry workers were determined firstly based on the database of the 'Workplace Environmental Monitoring Information Systems (WEMIS)' provided by Taiwan OSHA. Considering the existence of miss data, the reconstruction of historical exposure techniques were then used for completing the long-term exposure data for SEGs with routine operations. For SEGs with non-routine operations, exposure modeling techniques, together with their time/activity records, were adopted for determining their long-term exposure concentrations. The Bayesian decision analysis (BDA) was adopted for conducting exposure and health risk assessments for any given SEG in the petrochemical industry. The resultant excessive cancer risk was then used to determine the corresponding loss of quality-adjusted life expectancy (QALE). Results show that low average concentrations can be found for SEGs with routine operations (e.g., VCM rectification 0.0973 ppm, polymerization 0.306 ppm, reaction tank 0.33 ppm, VCM recovery 1.4 ppm, control room 0.14 ppm, VCM storage tanks 0.095 ppm and wastewater treatment 0.390 ppm), and the above values were much lower than that of the permissible exposure limit (PEL; 3 ppm) of VCM promulgated in Taiwan. For non-routine workers, though their high exposure concentrations, their low exposure time and frequencies result in low corresponding health risks. Through the consideration of exposure assessment results, health risk assessment results, and QALE results simultaneously, it is concluded that the proposed method was useful for prioritizing SEGs for conducting exposure abatement measurements. Particularly, the obtained QALE results further indicate the importance of reducing workers’ VCM exposures, though their exposures were low as in comparison with the PEL and the acceptable health risk.

Keywords: exposure assessment, health risk assessment, petrochemical industry, quality-adjusted life years, vinyl chloride monomer

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Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Azar Heidarizadi, Mahdieh Salimi, Hossein Mozdarani

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Introduction: As a complex disease, breast cancer results from several genetic and epigenetic changes. Lactoferrin, a member of the transferrin family, is reported to have a number of biological functions, including DNA synthesis, immune responses, iron transport, etc., any of which could play a role in tumor progression. The aim of this study was to investigate the bioinformatics data and experimental assay to find the pattern of promoter methylation and gene expression of LTF in breast cancer in order to study its potential role in cancer management. Material and Methods: In order to evaluate the methylation status of the LTF promoter, we studied the MS-PCR and Real-Time PCR on samples from patients with breast cancer and normal cases. 67 patient samples were conducted for this study, including tumoral, plasma, and normal tissue adjacent samples, as well as 30 plasma from normal cases and 10 tissue breast reduction cases. Subsequently, bioinformatics analyses such as cBioPortal databases, string, and genomatix were conducted to disclose the prognostic value of LTF in breast cancer progression. Results: The analysis of LTF expression showed an inverse relationship between the expression level of LTF and the stages of tissues of breast cancer patients (p<0.01). In fact, stages 1 and 2 had a high expression in LTF, while, in stages 3 and 4, a significant reduction was observable (p < 0.0001). LTF expression frequently alters with a decrease in the expression in ER⁺, PR⁺, and HER2⁺ patients (P < 0.01) and an increase in the expression in the TNBC, LN¯, ER¯, and PR- patients (P < 0.001). Also, LTF expression is significantly associated with metastasis and lymph node involvement factors (P < 0.0001). The sensitivity and specificity of LTF were detected, respectively. A negative correlation was detected between the results of level expression and methylation of the LTF promoter. Conclusions: The altered expression of LTF observed in breast cancer patients could be considered as a promotion in cell proliferation and metastasis even in the early stages of cancer.

Keywords: LTF, expression, methylation, breast cancer

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Dina Fatmawati, Sofia Mubarika, Mae Sri Wahyuningsih

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Chemotherapy for breast cancer is largely ineffective, but innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. In our previous study, the combination of Doxorubicin (Dox) and ethanolic extract of Dioscorea esculenta tuber ((EED) was found to have a synergistic effect on T47D human breast cancer cell line. In this study, we investigated the apoptotic effect of the combination on T47D human breast cancer cells and normal fibroblasts cell line and its effects on the expression of Caspase-3 and cleaved poly (ADP-Ribose) Polymerase-1 (cPARP-1) protein. T47D cell lines and fibroblasts cells were treated with the combination of Dox and EED. Apoptotic effect of the combination was determined using flow cytrometry assay. Protein expressions were determined by immunocytochemistry staining. The percentage of apoptotic cells were significantly higher in T47D cell lines (75%) than that of in fibroblast cells (23%). The expression of Caspase 3 (84.53%) and cPARP-1 (83.36%) were significantly higher in the cancer cell lines than those of normal cells. These results indicate that the combination of doxorubicin and Dioscorea esculenta is a promising candidate for the treatment of breast cancer cells.

Keywords: Dioscorea esculenta, Doxorubicin, apoptosis, immunocytochemistry, cancer cells

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Authors: Mahdiyeh Gholaminezhad

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Context: The study focuses on the potential impact of Sorafenib on SOAT1 protein in liver cancer treatment, addressing the need for more effective therapeutic options. Research aim: To explore the effects of Sorafenib on the activity of SOAT1 protein in liver cancer cells. Methodology: Molecular docking was employed to analyze the interaction between Sorafenib and SOAT1 protein. Findings: The study revealed a significant effect of Sorafenib on the stability and activity of SOAT1 protein, suggesting its potential as a treatment for liver cancer. Theoretical importance: This research highlights the molecular mechanism underlying Sorafenib's anti-cancer properties, contributing to the understanding of its therapeutic effects. Data collection: Data on the molecular structure of Sorafenib and SOAT1 protein were obtained from computational simulations and databases. Analysis procedures: Molecular docking simulations were performed to predict the binding interactions between Sorafenib and SOAT1 protein. Question addressed: How does Sorafenib influence the activity of SOAT1 protein and what are the implications for liver cancer treatment? Conclusion: The study demonstrates the potential of Sorafenib as a targeted therapy for liver cancer by affecting the activity of SOAT1 protein. Reviewers' Comments: The study provides valuable insights into the molecular basis of Sorafenib's action on SOAT1 protein, suggesting its therapeutic potential. To enhance the methodology, the authors could consider validating the docking results with experimental data for further validation.

Keywords: liver cancer, sorafenib, SOAT1, molecular docking

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Authors: Srisopa Ruangnoo, Arunporn Itharat

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The ethanolic and aqueous extracts of Parkia javanica Merr. germinating seeds and Parkia speciosa Hassk. seeds were evaluated for cytotoxic activity against three different types of human cancer cell lines including colon cancer (LS174T), breast cancer (MCF-7) and prostate cancer (PC3) using sulforhodamine B (SRB) assay. The fresh plant parts were divided into 2 parts. The first part was extracted by maceration with 95% ethanol for 3 days and then filtered, and the filtrates were evaporated by rotary evaporator. The other part was squeezed and filtered. Then the filtrates were dried by freeze dryer. The screening found that the aqueous extract of P. javanica Merr. germinating seeds exhibited more than 70% inhibition (at concentration 50 µg/ml) against all types of human cancer cells. The aqueous extract of P. javanica Merr. germinating seeds showed the highest cytotoxic activity against MCF-7 with the IC50 value as 5.63 µg/ml. The aqueous extract of P. javanica Merr. germinating seeds also showed high cytotoxic activity against PC3 and LS174T with the IC50 values as 10.79 and 11.40 µg/ml, respectively. In conclusion, P. javanica Merr. germinating seed is a natural source of anticancer activity and further research to isolate active compounds from this plant should be undertaken.

Keywords: cytotoxic activity, Parkia javanica Merr., Parkia speciosa Hassk., human cancer cell lines

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Authors: Afolabi K. Esther, Kuye Tolulope, Babafemi, L. Olayemi, Omikunle Yemisi

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Background: Cervical cancer is a potentially preventable disease of public significance. All sexually active women are at risk of cervical cancer; however, the uptake and coverage are low in low-middle resource countries. Hence, the programme explored the feasibility of demonstrating an innovative and low-cost system approach to cervical cancer screening service delivery among reproductive-aged women in low–resource settings in Southwestern Nigeria. This was to promote the uptake and quality improvement of cervical cancer screening services. Methods: This study was an intervention project in three senatorial districts in Osun State that have primary, secondary and tertiary health facilities. The project was in three phases; Pre-intervention, Intervention, and Post-intervention. The study utilised the existing infrastructure, facilities and staff in project settings. The study population was nurse-midwives, community health workers and reproductive-aged women (30-49 years). The intervention phase entailed using innovative, culturally appropriate strategies to create awareness of cervical cancer and preventive health-seeking behaviour among women in the reproductive-aged group (30-49) years. Also, the service providers (community health workers, Nurses, and Midwives) were trained on screening methods and treatment of pre-cancerous lesions, and there was the provision of essential equipment and supplies for cervical cancer screening services at health facilities. Besides, advocacy and engagement were made with relevant stakeholders to integrate the cervical cancer screening services into related reproductive health services and greater allocation of resources. The expected results compared the pre and post-intervention using the baseline and process indicators and the effect of the intervention phase on screening coverage using a plausibility assessment design. The project lasted 12 months; visual Inspection with Acetic acid (VIA) screening for the women for six months and follow-up in 6 months for women receiving treatment. Results: The pre-intervention phase assessed baseline service delivery statistics in the previous 12 months drawn from the retrospective data collected as part of the routine monitoring and reporting systems. The uptake of cervical cancer screening services was low as the number of women screened in the previous 12 months was 156. Service personnel's competency level was fair (54%), and limited availability of essential equipment and supplies for cervical cancer screening services. At the post-intervention phase, the level of uptake had increased as the number of women screened was 1586 within six months in the study settings. This showed about a 100-%increase in the uptake of cervical cancer screening services compared with the baseline assessment. Also, the post-intervention level of competency of service delivery personnel had increased to 86.3%, which indicates quality improvement of the cervical cancer screening service delivery. Conclusion: the findings from the study have shown an effective approach to strengthening and improving cervical cancer screening service delivery in Southwestern Nigeria. Hence, the intervention promoted a positive attitude and health-seeking behaviour among the target population, significantly influencing the uptake of cervical cancer screening services.

Keywords: cervical cancer, screening, nigeria, health system strengthening

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

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At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

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Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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Authors: Christo Februanto Putra

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This paper presents risk identification that affects investment feasibility on toll road infrastructure in Indonesia using qualitative methods survey based on the expert practitioner in investor, contractor, and state officials. The problems on infrastructure investment in Indonesia, especially on KPBU model contract, is many risk factors in the investment plan is not calculated in detail thoroughly. Risk factor is a value used to provide an overview of the risk level assessment of an event which is a function of the probability of the occurrence and the consequences of the risks that arise. As results of the survey which is to show which risk factors impacts directly to the investment feasibility and rank them by their impacts on the investment.

Keywords: risk identification, indonesia toll road, investment feasibility

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Authors: Wenxing Chen, Guangying Chen, Yin Lu, Shile Huang

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Cryptotanshinone (CPT), a fat-soluble tanshinone from Salvia miltiorrhiza Bunge, has been demonstrated to inhibit mTOR pathway, resulting in inhibition of cancer cell proliferation. However, the molecular mechanism how CPT acts on mTOR is unknown. Here, cancer cells expressing rapamycin-resistant mutant mTOR are also sensitive to CPT, while phosphorylation of AMPK and TSC2 was activated, suggesting that CPT inhibition of mTOR maybe due to activating upstream of mTOR, AMPK, but not directly binding to and inhibiting mTOR. Further results indicated that Compound C, inhibitor of AMPK, could partially reversed CPT inhibition effect on cancer cells, and dominant-negative AMPK in cancer cells conferred resistance to CPT inhibition of 4EBP1 and phosphorylation of S6K1, as well as sh-AMPK. Furthermore, compared with MEF cells with AMPK positive, MEF cells with AMPK knock out are less sensitive to CPT by the findings that 4E-BP1 and phosphorylation of S6K1 express comparatively much. Furthermore, downexpression of TSC2 slightly recovered expression of 4EBP1 and phosphorylation of S6K1, while co-immunoprecipitation of TSC2 did not affect expression of TSC1 by CPT. Collectively, the above-mentioned results suggest that CPT inhibited mTOR pathway mostly was due to activation of AMPK-TSC2 pathway rather than specific inhibition of mTOR and then induction of subsequent lethal cellular effect.

Keywords: cryptotanshinone, AMPK, TSC2, mTOR, cancer cells

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Authors: T. Al-Alawi, N. Shorbaji, E. Rashaidi, M.Alidrisi

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Purpose/Objective(s): The main purpose of this study is to analyze the planning of SBRT treatments for localized prostate cancer with 6FFF and 10FFF energies to see if there is a dosimetric difference between the two energies and how we can increase the plan efficiency and reduce its complexity. Also, to introduce a planning method in our department to treat prostate cancer by utilizing high energy photons without increasing patient toxicity and fulfilled all dosimetric constraints for OAR (an organ at risk). Then toevaluate the target 95% coverage PTV95, V5%, V2%, V1%, low dose volume for OAR (V1Gy, V2Gy, V5Gy), monitor unit (beam-on time), and estimate the values of homogeneity index HI, conformity index CI a Gradient index GI for each treatment plan.Materials/Methods: Two treatment plans were generated for15 patients with localized prostate cancer retrospectively using the CT planning image acquired for radiotherapy purposes. Each plan contains two/three complete arcs with two/three different collimator angle sets. The maximum dose rate available is 1400MU/min for the energy 6FFF and 2400MU/min for 10FFF. So in case, we need to avoid changing the gantry speed during the rotation, we tend to use the third arc in the plan with 6FFF to accommodate the high dose per fraction. The clinical target volume (CTV) consists of the entire prostate for organ-confined disease. The planning target volume (PTV) involves a margin of 5 mm. A 3-mm margin is favored posteriorly. Organs at risk identified and contoured include the rectum, bladder, penile bulb, femoral heads, and small bowel. The prescription dose is to deliver 35Gyin five fractions to the PTV and apply constraints for organ at risk (OAR) derived from those reported in references. Results: In terms of CI=0.99, HI=0.7, and GI= 4.1, it was observed that they are all thesame for both energies 6FFF and 10FFF with no differences, but the total delivered MUs are much less for the 10FFF plans (2907 for 6FFF vs.2468 for 10FFF) and the total delivery time is 124Sc for 6FFF vs. 61Sc for 10FFF beams. There were no dosimetric differences between 6FFF and 10FFF in terms of PTV coverage and mean doses; the mean doses for the bladder, rectum, femoral heads, penile bulb, and small bowel were collected, and they were in favor of the 10FFF. Also, we got lower V1Gy, V2Gy, and V5Gy doses for all OAR with 10FFF plans. Integral dosesID in (Gy. L) were recorded for all OAR, and they were lower with the 10FFF plans. Conclusion: High energy 10FFF has lower treatment time and lower delivered MUs; also, 10FFF showed lower integral and meant doses to organs at risk. In this study, we suggest usinga 10FFF beam for SBRTprostate treatment, which has the advantage of lowering the treatment time and that lead to lessplan complexity with respect to 6FFF beams.

Keywords: FFF beam, SBRT prostate, VMAT, prostate cancer

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Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

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Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Emad A. Shalaby

Abstract:

Cancer is a disease that causes abnormal cell proliferation and invades nearby tissues. Lung cancer is the second most frequent cancer worldwide. Natural anti-cancer drugs have been developed with low side effects and toxicity. Citrus peels and extracts have been demonstrated to have significant pharmacological and physiological effects as a result of the high concentration of phenolic compounds found in citrus fruits, particularly peels. Tangerine peels can serve as an effective source of bioactive substances such as phenolics, flavonoids, and catechins, which have antioxidant, antibacterial, anticancer, and anti-inflammatory properties. Consequently, this work aims to determine the anticancer activity of ethanol extract of Tangerine peels against the A549 cell line and identify the phenolic compound profile (19 compounds) by using HPLC. Anticancer and antioxidant potentials of the extract were evaluated by MTT assay and TLC- TLC-bioautography sprayed with DPPH reagent, respectively. The obtained results revealed that tangerine peel extract showed significant activity against the A549 cell line with IC50 of 97.66 μg/mL. HPLC analysis proved that the highest concentration is naringenin 464.05 mg/g. More studies indicate that naringenin has significant anticancer potential on A549 cancer cells. The results showed that naringenin binds t0 EGFR protein in A549 with high binding affinity and thus may reduce lung cancer cell migration and enhance the apoptosis of cancer cells. From the obtained results it could be concluded that tangerine peel extract is an effective anti-cancer agent that may potentially serve as a natural therapeutic option for lung cancer treatment.

Keywords: tangerine peel, A549 cell line, anticancer, naringenin, HPLC analysis, naringenin, TLC bioautography

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Authors: Janusz K. Grabara, Bartłomiej Okwiet, Sebastian Kot

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The purpose of the article is presentation and analysis of the aspect of job security in small and medium-size enterprises in Poland with reference to other EU countries. We show the theoretical aspects of the risk with reference to managing small and medium enterprises, next risk management in small and medium enterprises in Poland, which were subjected to a detailed analysis. We show in detail the risk associated with the operation of the mentioned above companies, as well as analyses its levels on various stages and for different kinds of conducted activity.

Keywords: job safety, SME, work risk, risk management

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Jeena R. S., Sukesh Kumar A.

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Stroke is one of the major reasons of adult disability and morbidity in many of the developing countries like India. Early diagnosis of stroke is essential for timely prevention and cure. Various conventional statistical methods and computational intelligent models have been developed for predicting the risk and outcome of stroke. This research work focuses on a multilevel approach for predicting the occurrence of stroke based on various risk factors and invasive techniques like retinal imaging. This risk prediction model can aid in clinical decision making and help patients to have an improved and reliable risk prediction.

Keywords: prediction, retinal imaging, risk factors, stroke

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Authors: Cecília M. Antão, Paulo Jorge Nogueira

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Breast cancer (BC) is the first cause of cancer mortality among Portuguese women. This retrospective observational study aimed at identifying comorbidities associated with BC female patients admitted to Portuguese public hospitals (2010-2018), investigating the effect of comorbidities on BC mortality rate, and building a predictive model using logistic regression. Results showed that the BC mortality in Portugal decreased in this period and reached 4.37% in 2018. Adjusted odds ratio indicated that secondary malignant neoplasms of liver, of bone and bone marrow, congestive heart failure, and diabetes were associated with an increased chance of dying from breast cancer. Although the Lisbon district (the most populated area) accounted for the largest percentage of BC patients, the logistic regression model showed that, besides patient’s age, being resident in Bragança, Castelo Branco, or Porto districts was directly associated with an increase of the mortality rate.

Keywords: breast cancer, comorbidities, logistic regression, adjusted odds ratio

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Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

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Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

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Authors: Dipali Dhawan

Abstract:

Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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