Cancer Informatics最新文献

{"title":"Computational Identification of Stearic Acid as a Potential PDK1 Inhibitor and In Vitro Validation of Stearic Acid as Colon Cancer Therapeutic in Combination with 5-Fluorouracil.","authors":"Jonathan Mitchel,&nbsp;Pratima Bajaj,&nbsp;Ketki Patil,&nbsp;Austin Gunnarson,&nbsp;Emilie Pourchet,&nbsp;Yoo Na Kim,&nbsp;Jeffrey Skolnick,&nbsp;S Balakrishna Pai","doi":"10.1177/11769351211065979","DOIUrl":"https://doi.org/10.1177/11769351211065979","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is the third largest cause of cancer-related mortality worldwide. Although current treatments with chemotherapeutics have allowed for management of colorectal cancer, additional novel treatments are essential. Intervening with the metabolic reprogramming observed in cancers called \"Warburg Effect,\" is one of the novel strategies considered to combat cancers. In the metabolic reprogramming pathway, pyruvate dehydrogenase kinase (PDK1) plays a pivotal role. Identification and characterization of a PDK1 inhibitor is of paramount importance. Further, for efficacious treatment of colorectal cancers, combinatorial regimens are essential. To this end, we opted to identify a PDK1 inhibitor using computational structure-based drug design FINDSITE^comb and perform combinatorial studies with 5-FU for efficacious treatment of colorectal cancers.</p><p><strong>Methods: </strong>Using computational structure-based drug design FINDSITE^comb, stearic acid (SA) was identified as a possible PDK1 inhibitor. Elucidation of the mechanism of action of SA was performed using flow cytometry, clonogenic assays.</p><p><strong>Results: </strong>When the growth inhibitory potential of SA was tested on colorectal adenocarcinoma (DLD-1) cells, a 50% inhibitory concentration (IC₅₀) of 60 µM was recorded. Moreover, SA inhibited the proliferation potential of DLD-1 cells as shown by the clonogenic assay and there was a sustained response even after withdrawal of the compound. Elucidation of the mechanism of action revealed, that the inhibitory effect of SA was through the programmed cell death pathway. There was increase in the number of apoptotic and multicaspase positive cells. SA also impacted the levels of the cell survival protein Bcl-2. With the aim of achieving improved treatment for colorectal cancer, we opted to combine 5-fluorouracil (5-FU), the currently used drug in the clinic, with SA. Combining SA with 5-FU, revealed a synergistic effect in which the IC₅₀ of 5-FU decreased from 25 to 6 µM upon combination with 60 µM SA. Further, SA did not inhibit non-tumorigenic NIH-3T3 proliferation.</p><p><strong>Conclusions: </strong>We envision that this significant decrease in the IC₅₀ of 5-FU could translate into less side effects of 5-FU and increase the efficacy of the treatment due to the multifaceted action of SA. The data generated from the current studies on the inhibition of colorectal adenocarcinoma by SA discovered by the use of the computational program as well as synergistic action with 5-FU should open up novel therapeutic options for the management of colorectal adenocarcinomas.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211065979"},"PeriodicalIF":2.0,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/cb/10.1177_11769351211065979.PMC8679029.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39738465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sparse Regression in Cancer Genomics: Comparing Variable Selection and Predictions in Real World Data.","authors":"Robert J O'Shea, Sophia Tsoka, Gary Jr Cook, Vicky Goh","doi":"10.1177/11769351211056298","DOIUrl":"10.1177/11769351211056298","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Evaluation of gene interaction models in cancer genomics is challenging, as the true distribution is uncertain. Previous analyses have benchmarked models using synthetic data or databases of experimentally verified interactions - approaches which are susceptible to misrepresentation and incompleteness, respectively. The objectives of this analysis are to (1) provide a real-world data-driven approach for comparing performance of genomic model inference algorithms, (2) compare the performance of LASSO, elastic net, best-subset selection, &lt;math&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/mrow&gt; &lt;/math&gt; penalisation and &lt;math&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/mrow&gt; &lt;/math&gt; penalisation in real genomic data and (3) compare algorithmic preselection according to performance in our benchmark datasets to algorithmic selection by internal cross-validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Five large &lt;math&gt;&lt;mrow&gt;&lt;mo&gt;(&lt;/mo&gt; &lt;mi&gt;n&lt;/mi&gt; &lt;mn&gt;4000&lt;/mn&gt; &lt;mo&gt;)&lt;/mo&gt;&lt;/mrow&gt; &lt;/math&gt; genomic datasets were extracted from Gene Expression Omnibus. 'Gold-standard' regression models were trained on subspaces of these datasets ( &lt;math&gt;&lt;mrow&gt;&lt;mi&gt;n&lt;/mi&gt; &lt;mn&gt;4000&lt;/mn&gt;&lt;/mrow&gt; &lt;/math&gt; , &lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;500&lt;/mn&gt;&lt;/mrow&gt; &lt;/math&gt; ). Penalised regression models were trained on small samples from these subspaces ( &lt;math&gt;&lt;mrow&gt;&lt;mi&gt;n&lt;/mi&gt; &lt;mo&gt;∈&lt;/mo&gt; &lt;mrow&gt;&lt;mo&gt;{&lt;/mo&gt; &lt;mrow&gt;&lt;mn&gt;25&lt;/mn&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;75&lt;/mn&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mn&gt;150&lt;/mn&gt;&lt;/mrow&gt; &lt;mo&gt;}&lt;/mo&gt;&lt;/mrow&gt; &lt;mo&gt;,&lt;/mo&gt; &lt;mi&gt;p&lt;/mi&gt; &lt;mo&gt;=&lt;/mo&gt; &lt;mn&gt;500&lt;/mn&gt;&lt;/mrow&gt; &lt;/math&gt; ) and validated against the gold-standard models. Variable selection performance and out-of-sample prediction were assessed. Penalty 'preselection' according to test performance in the other 4 datasets was compared to selection internal cross-validation error minimisation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;math&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;1&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/mrow&gt; &lt;/math&gt; -penalisation achieved the highest cosine similarity between estimated coefficients and those of gold-standard models. &lt;math&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/mrow&gt; &lt;/math&gt; -penalised models explained the greatest proportion of variance in test responses, though performance was unreliable in low signal:noise conditions. &lt;math&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;msub&gt;&lt;mi&gt;L&lt;/mi&gt; &lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;/mrow&gt; &lt;/math&gt; also attained the highest overall median variable selection F1 score. Penalty preselection significantly outperformed selection by internal cross-validation in each of 3 examined metrics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This analysis explores a novel approach for comparisons of model selection approaches in real genomic data from 5 cancers. Our benchma","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211056298"},"PeriodicalIF":2.0,"publicationDate":"2021-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39693077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of melatonin on the Bisphenol-A- induced cytotoxicity and genetic toxicity in colon cancer cell lines, normal gingival cell lines, and bone marrow stem cell lines.","authors":"Rouya Ebrahimi,&nbsp;Mohammad Shokrzadeh,&nbsp;Nasrin Ghassemi Barghi","doi":"10.1177/11769351211056295","DOIUrl":"https://doi.org/10.1177/11769351211056295","url":null,"abstract":"<p><p>Bisphenol-A (BPA) is a synthetic chemical that has widely been used in the production of polycarbonate plastic and epoxy resins in the manufacture of consumer products. The most common path of human exposure to BPA is by oral intake that involves genotoxicity, oxidative stress, endocrine disruption, mutagenicity, and carcinogenicity in both <i>in vitro</i> and <i>in vivo</i> models. Melatonin is known as a free-radical scavenger and a powerful antioxidant agent. This study aimed to investigate the effects of melatonin on viability and genetic disorders of normal Human Gingival Fibroblasts (HGF), colon cancer (MKN45), and bone marrow stem cell (MSC) lines exposed to BPA. For this purpose, MTT and Comet assays were performed to evaluate the cytotoxicity and genotoxicity properties of BPA and the role of melatonin. The results showed that BPA exposure resulted in increased oxidative stress parameters including MDA and ROS, and decreased GSH content. The current study demonstrated the cytotoxicity and genotoxicity effects of BPA and the protective role of melatonin in preventing cytotoxicity and DNA damage are induced by BPA.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211056295"},"PeriodicalIF":2.0,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/5b/10.1177_11769351211056295.PMC8606939.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39655635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of Selected Flavonoid Structures and Their Potential Activity as Breast Anticancer Agents.","authors":"Mohammed Hadi Ali Al-Jumaili,&nbsp;Muqdad Khairi Yahya Al Hdeethi","doi":"10.1177/11769351211055160","DOIUrl":"https://doi.org/10.1177/11769351211055160","url":null,"abstract":"<p><p>Flavonoids contain pharmacological effects that help to protect cells from damage. However, the anticancer activity of flavonoids is related to their modulation of signal transduction pathways within cancer cells. Natural substances such as flavonoids have immune-stimulating anti-tumor effect that could lower breast cancer risk. However, various diseases included Alzheimer's and cancer disease are associated with flavonoids intake due to their ability as antioxidant agent to alter essential cellular enzyme's function. Therefore, through interaction between flavonoids and Cytochrome P450 (CYP) family enzymes led to make them chemopreventive agents for breast cancer. In this analysis, the chemo-informatics properties of 5 selective flavonoid derivatives and their efficiency as anti-breast cancer drugs were evaluated. Flavonoid ligands were docked with the predicted protein, which is human placental aromatase complexes with exemestane, a breast cancer drug (3S7S). Based on various docking energies, the molecular characteristics and bioactivity score of the following components, C₁₅H₁₂O₆ 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydro-4H-chromen-4-one and C₁₅H₁₂O₅ 5,8-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one showed greatest molecular properties and bioactivity docking scores of -8.633117 and -8.633117 kcal/mol respectively. Therefore, both compounds could be considered antitumor agent.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211055160"},"PeriodicalIF":2.0,"publicationDate":"2021-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/27/10.1177_11769351211055160.PMC8597067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39642924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Aneuploidy Spectrum From Whole-Genome Sequencing Provides Rapid Assessment of Clonal Variation Within Established Cancer Cell Lines.","authors":"Ahmed Ibrahim Samir Khalil,&nbsp;Anupam Chattopadhyay,&nbsp;Amartya Sanyal","doi":"10.1177/11769351211049236","DOIUrl":"10.1177/11769351211049236","url":null,"abstract":"<p><strong>Background: </strong>The revolution in next-generation sequencing (NGS) technology has allowed easy access and sharing of high-throughput sequencing datasets of cancer cell lines and their integrative analyses. However, long-term passaging and culture conditions introduce high levels of genomic and phenotypic diversity in established cell lines resulting in strain differences. Thus, clonal variation in cultured cell lines with respect to the reference standard is a major barrier in systems biology data analyses. Therefore, there is a pressing need for a fast and entry-level assessment of clonal variations within cell lines using their high-throughput sequencing data.</p><p><strong>Results: </strong>We developed a Python-based software, AStra, for <i>de novo</i> estimation of the genome-wide segmental aneuploidy to measure and visually interpret strain-level similarities or differences of cancer cell lines from whole-genome sequencing (WGS). We demonstrated that aneuploidy spectrum can capture the genetic variations in 27 strains of MCF7 breast cancer cell line collected from different laboratories. Performance evaluation of AStra using several cancer sequencing datasets revealed that cancer cell lines exhibit distinct aneuploidy spectra which reflect their previously-reported karyotypic observations. Similarly, AStra successfully identified large-scale DNA copy number variations (CNVs) artificially introduced in simulated WGS datasets.</p><p><strong>Conclusions: </strong>AStra provides an analytical and visualization platform for rapid and easy comparison between different strains or between cell lines based on their aneuploidy spectra solely using the raw BAM files representing mapped reads. We recommend AStra for rapid first-pass quality assessment of cancer cell lines before integrating scientific datasets that employ deep sequencing. AStra is an open-source software and is available at https://github.com/AISKhalil/AStra.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211049236"},"PeriodicalIF":2.0,"publicationDate":"2021-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/46/10.1177_11769351211049236.PMC8521761.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39561135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymph Node Ratio after Neoadjuvant Chemotherapy for Stage II/III Breast Cancer: Prognostic Value Measured with Gini's Mean Difference of Restricted Mean Survival Times.","authors":"Bhumsuk Keam,&nbsp;Olena Gorobets,&nbsp;Vincent Vinh-Hung,&nbsp;Seock-Ah Im","doi":"10.1177/11769351211051675","DOIUrl":"https://doi.org/10.1177/11769351211051675","url":null,"abstract":"<p><p>Restricted mean survival time (RMST), recommended for reporting survival, lacks a tool to evaluate multilevel factors. The potential of the Gini's mean difference of RMSTs (Δ) is explored in a comparison of a lymph node ratio-based classification (LNRc) versus a number-based classification (ypN) applied to stage II/III breast cancer patients who received neoadjuvant chemotherapy and underwent axillary dissection. Number of positive nodes (<i>npos</i>) classified patients into ypN0, <i>npos</i> = 0, ypN1, <i>npos</i> = [1,3], ypN2, <i>npos</i> = [4,9], and ypN3, <i>npos</i> ⩾ 10. Ratio <i>npos</i>/(<i>number of nodes examined</i>) of 0, (0,0.20], (0.20,0.65], and >0.65, classified patients into Lnr0 to Lnr3, respectively. Unadjusted and Cox-adjusted RMSTs were computed for the ypN and LNRc's. At a follow-up time horizon of 72 months for 114 node-negative and 254 node-positive patients, unadjusted ypN0-ypN3 RMSTs were 62.4-41.4 months, Δ = 11.9 months (95%CI: 7.4-16.9), and Lnr0-Lnr3 62.4 to 36.3 months, Δ = 14.0 months (95%CI: 10.1-18.1). Cox models' ypN1-ypN3 hazard ratios were 1.81-3.30, and Lnr1-Lnr3 1.52-4.39. Δ from Cox-fitted survival were ypN 8.1 months (95%CI: 5.9-10.5), LNRc 10.5 months (95%CI: 8.4-12.8). In conclusion, Gini's mean difference is applicable to well established data in keeping with the literature on LNRc. It provides an alternative view on the improvement gained with a lymph node ratio-classification over using a number-classification.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211051675"},"PeriodicalIF":2.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/f3/10.1177_11769351211051675.PMC8521726.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39537806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Evaluation of Bioactive Compounds from <i>Colocasia affinis</i> Schott as a Novel EGFR Inhibitor for Cancer Treatment.","authors":"Toheeb A Balogun, Nureni Ipinloju, Olayemi T Abdullateef, Segun I Moses, Damilola A Omoboyowa, Akinwumi C James, Oluwatosin A Saibu, Wumi F Akinyemi, Ebenezer A Oni","doi":"10.1177/11769351211049244","DOIUrl":"10.1177/11769351211049244","url":null,"abstract":"<p><strong>Introduction: </strong>Epidermal growth factor receptor (EGFR) is a transmembrane protein that belongs to the ErbB/HER-family of tyrosine kinase receptors. Somatic mutations and overexpression of EGFR have been reported to play a vital role in cancer cell development and progression, including cell proliferation, differentiation, angiogenesis, apoptosis, and metastatic spread. Hence, EGFR is an important therapeutic target for the treatment of various types of epithelial cancers. Somatic mutations have led to resistance to clinically approved synthetic EGFR inhibitors. Furthermore, synthetic EGFR inhibitors have been associated with several side effects. Thus, there is a need to develop novel EGFR inhibitors with an acceptable biosafety profile and high efficacy.</p><p><strong>Methods: </strong>Herein, we employed structural bioinformatics and theoretical chemistry techniques via molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) calculation, density functional theory analysis (DFT), and pharmacokinetic study to identify novel EGFR inhibitors.</p><p><strong>Results: </strong>The stringent molecular docking and MM-GBSA calculations identified MET 793, LYS 745, PHE 723, ASP 855, ARG 411, and THR 854 as principal amino acid residues for EGFR-ligands interactions. Furthermore, <i>Colocasia affinis</i> Schott compounds exhibited higher binding energy and more stable interactions than the reference compound (gefitinib). DFT analysis also ascertains better bioactivity and chemical reactivity of <i>C. affinis</i> Schott with favorable intramolecular charge transfer between electron-donor and electron acceptor groups. The pharmacokinetic profile of <i>C. affinis</i> Schott bioactive compounds satisfies Lipinski's rule of five assessment.</p><p><strong>Conclusion: </strong>Collectively, <i>C. affinis</i> Schott compounds demonstrated higher inhibitory potentials against EGFR and better pharmacological properties when compared with gefitinib. <i>C. affinis</i> Schott compounds are therefore suggested as promising therapeutic EGFR inhibitors for cancer treatment.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211049244"},"PeriodicalIF":2.0,"publicationDate":"2021-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/dc/10.1177_11769351211049244.PMC8504293.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39515059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature","authors":"K. Wager, Dheepa Chari, Steffan Ho, Tomas J Rees, O. Penner, B. Schijvenaars","doi":"10.1177/11769351221086441","DOIUrl":"https://doi.org/10.1177/11769351221086441","url":null,"abstract":"Biomarkers, as measurements of defined biological characteristics, can play a pivotal role in estimations of disease risk, early detection, differential diagnosis, assessment of disease progression and outcomes prediction. Studies of cancer biomarkers are published daily; some are well characterized, while others are of growing interest. Managing this flow of information is challenging for scientists and clinicians. We sought to develop a novel text-mining method employing biomarker co-occurrence processing applied to a deeply indexed full-text database to generate time-interval–delimited biomarker co-occurrence networks. Biomarkers across 6 cancer sites and a cancer-agnostic network were successfully characterized in terms of their emergence in the published literature and the context in which they are described. Our approach, which enables us to find publications based on biomarker relationships, identified biomarker relationships not known to existing interaction networks. This search method finds relevant literature that could be missed with keyword searches, even if full text is available. It enables users to extract relevant biological information and may provide new biological insights that could not be achieved by individual review of papers.","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48923870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of Intraocular Pressure and Time to Blindness for Glaucoma Patients at Felege Hiwot Referral Hospital, Bahir Bar, Ethiopia: A Comparison of Separate and Joint Models.","authors":"Mitiku Wale Muluneh,&nbsp;Awoke Seyoum Tegegne","doi":"10.1177/11769351211045975","DOIUrl":"https://doi.org/10.1177/11769351211045975","url":null,"abstract":"<p><strong>Background: </strong>Due to the substantial increase in the number of glaucoma cases within the next several decades, glaucoma is a significant public health issue. The main objective of this study was to investigate the determinant factors of intraocular pressure and time to blindness of glaucoma patients under treatment at Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia.</p><p><strong>Methods: </strong>A retrospective study design was conducted on 328 randomly selected glaucoma patients using simple random sampling based on the identification number of patients in an ophthalmology clinic at the hospital under the follow-up period from January 2014 to December 2018. A linear mixed effects model for intraocular pressure data, a semi-parametric survival model for the time-to-blindness data and joint modeling of the 2 responses were used for data analysis. However, the primary outcome was survival time of glaucoma patients.</p><p><strong>Results: </strong>The comparison of joint and separate models revealed that joint model was more adequate and efficient inferences because of its smaller standard errors in parameter estimations. This was also approved using AIC, BIC, and based on a significant likelihood ratio test as well. The estimated association parameter (α) in the joint model was .0160 and statistically significant (<i>P</i>-value = .0349). This indicated that there was strong evidence for positive association between the effects of intraocular pressure and the risk of blindness. The result indicated that the higher value of intraocular pressure was associated with the higher risk of blindness. Age, hypertension, type of medication, cup-disk ratio significantly affects both average intraocular pressure and survival time of glaucoma patients (<i>P</i>-value < .05).</p><p><strong>Conclusion: </strong>The predictors; age, hypertension, type of medication, and cup-disk ratio were significantly associated with the 2 responses of glaucoma patients. Health professionals give more attention to patients who have blood pressure and cup-disk ratio greater than 0.7 during the follow-up time to reduce the risk of blindness of glaucoma patients.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211045975"},"PeriodicalIF":2.0,"publicationDate":"2021-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/81/10.1177_11769351211045975.PMC8450691.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39461895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Methyltransferases Useful in Gastric Cancer Research.","authors":"Dafne Alejandra Reyes,&nbsp;Victor Manuel Saure Sarría,&nbsp;Marcela Salazar-Viedma,&nbsp;Vívian D'Afonseca","doi":"10.1177/11769351211039862","DOIUrl":"https://doi.org/10.1177/11769351211039862","url":null,"abstract":"<p><p>Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients' clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the <i>PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3</i>, and <i>EHMT2</i> genes. The <i>PRDM9</i> gene is among most mutated and amplified HMTs within the data set studied. <i>PRDM14</i> is downregulated in 79% of the samples and the <i>SUV39H2</i> gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"20 ","pages":"11769351211039862"},"PeriodicalIF":2.0,"publicationDate":"2021-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/4b/10.1177_11769351211039862.PMC8369960.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39327872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}