Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118120030 ◽

2019 ◽

Vol 19 (8) ◽

pp. 1037-1047 ◽

Cited By ~ 2

Author(s):

Jihene Elloumi-Mseddi ◽

Dhouha Msalbi ◽

Raouia Fakhfakh ◽

Sami Aifa

Keyword(s):

Side Effects ◽

Anticancer Drugs ◽

Tumour Cell ◽

Caspase 3 ◽

Drug Repositioning ◽

Brdu Incorporation ◽

Drug Concentrations ◽

Significant Difference ◽

Ic50 Values ◽

Mcf 7

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.

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Ocean fertilization: a potential means of geoengineering?

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2008.0139 ◽

2008 ◽

Vol 366 (1882) ◽

pp. 3919-3945 ◽

Cited By ~ 93

Author(s):

R.S Lampitt ◽

E.P Achterberg ◽

T.R Anderson ◽

J.A Hughes ◽

M.D Iglesias-Rodriguez ◽

...

Keyword(s):

Side Effects ◽

Large Scale ◽

Biological Productivity ◽

Viable Option ◽

Address Climate Change ◽

Specific Objective ◽

Limiting Nutrients ◽

Level Of Knowledge ◽

Sound Foundation ◽

Change Mitigation

The oceans sequester carbon from the atmosphere partly as a result of biological productivity. Over much of the ocean surface, this productivity is limited by essential nutrients and we discuss whether it is likely that sequestration can be enhanced by supplying limiting nutrients. Various methods of supply have been suggested and we discuss the efficacy of each and the potential side effects that may develop as a result. Our conclusion is that these methods have the potential to enhance sequestration but that the current level of knowledge from the observations and modelling carried out to date does not provide a sound foundation on which to make clear predictions or recommendations. For ocean fertilization to become a viable option to sequester CO 2 , we need more extensive and targeted fieldwork and better mathematical models of ocean biogeochemical processes. Models are needed both to interpret field observations and to make reliable predictions about the side effects of large-scale fertilization. They would also be an essential tool with which to verify that sequestration has effectively taken place. There is considerable urgency to address climate change mitigation and this demands that new fieldwork plans are developed rapidly. In contrast to previous experiments, these must focus on the specific objective which is to assess the possibilities of CO 2 sequestration through fertilization.

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Building Anticancer Drugs Without Side Effects

ChemViews ◽

10.1002/chemv.201400003 ◽

2014 ◽

Author(s):

David Bradley

Keyword(s):

Side Effects ◽

Anticancer Drugs

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Efficacy of ultra-low-dose (0.1 mg) ranibizumab intravitreal injection for treatment of prethreshold type 1 retinopathy of prematurity: A case series

European Journal of Ophthalmology ◽

10.1177/1120672118812266 ◽

2018 ◽

Vol 30 (1) ◽

pp. 40-47 ◽

Cited By ~ 2

Author(s):

Islam SH Ahmed ◽

Ahmed MA Hadi ◽

Hassan H Hassan

Keyword(s):

Side Effects ◽

Intravitreal Injection ◽

Retinopathy Of Prematurity ◽

Large Scale ◽

Low Dose ◽

Case Series ◽

Results Of Treatment ◽

Case Series Study ◽

Systemic Side Effects

Aim: To report the results of treatment of type 1 prethreshold retinopathy of prematurity using intravitreal injection of ultra-low dose of ranibizumab (0.1 mg in 0.01 mL). Design: A retrospective observational case series study. Methods: Review of files of eligible infants who received this form of treatment to determine the outcome of treatment and any associated ocular or systemic side effects. Results: The study included 24 eyes of 12 preterm infants with mean gestational age of 29.75 ± 1.54 weeks and mean birth weight of 1074.58 ± 320.59 g. A total of 22 eyes (91.67%) had zone II disease while 2 eyes of one infant (8.33%) had zone I disease. All cases showed regression of the signs of the active retinopathy of prematurity with complete retinal vascularization. None of the cases required retreatment. Three eyes developed ocular complications. Apart from mild feeding intolerance that lasted for 24 h after injection in one infant, none of the cases developed systemic side effects. Conclusion: Intravitreal injection of ultra-low-dose ranibizumab showed promising efficacy and good ocular safety. However, further large-scale studies are required to give stronger evidence about the efficacy and safety of ultra-low-dose ranibizumab.

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PaperBLAST: Text-mining papers for information about homologs

10.1101/133041 ◽

2017 ◽

Author(s):

Morgan N. Price ◽

Adam P. Arkin

Keyword(s):

Text Mining ◽

Genome Sequencing ◽

Full Text ◽

Large Scale ◽

Scientific Literature ◽

Protein Sequences ◽

Protein Coding ◽

Link Protein ◽

Protein Coding Genes ◽

Link Type

AbstractLarge-scale genome sequencing has identified millions of protein-coding genes whose function is unknown. Many of these proteins are similar to characterized proteins from other organisms, but much of this information is missing from annotation databases and is hidden in the scientific literature. To make this information accessible, PaperBLAST uses EuropePMC to search the full text of scientific articles for references to genes. PaperBLAST also takes advantage of curated resources that link protein sequences to scientific articles (Swiss-Prot, GeneRIF, and EcoCyc). PaperBLAST’s database includes over 700,000 scientific articles that mention over 400,000 different proteins. Given a protein of interest, PaperBLAST quickly finds similar proteins that are discussed in the literature and presents snippets of text from relevant articles or from the curators. PaperBLAST is available at http://papers.genomics.lbl.gov/.

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Thrombolytic Therapy in the Acute Period of Aortic Thromboembolism in Cats

Veterinary Evidence ◽

10.18849/ve.v4i2.212 ◽

2019 ◽

Vol 4 (2) ◽

Author(s):

Joshua Billy Hannabuss

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Open Access ◽

Thrombolytic Therapy ◽

Acute Phase ◽

Large Scale ◽

Supportive Therapy ◽

Controlled Clinical Trials ◽

Bottom Line ◽

Adverse Side Effects

PICO question Of cats that present with aortic thromboembolism, do patients that receive thrombolytic therapy in the acute phase have improved survival as compared to those who do not?Clinical bottom line Based on the current available evidence, the use of thrombolytic therapy in the acute phase of aortic thromboembolism (ATE) does not appear to improve survival when compared to conventional supportive therapy. Frequently reported adverse side effects further questions its merits, and large scale controlled clinical trials would be required to further evaluate any benefit in the use of this therapy. <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" />

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Side Effects of mRNA-Based COVID-19 Vaccine: Nationwide Phase IV Study among Healthcare Workers in Slovakia

Pharmaceuticals ◽

10.3390/ph14090873 ◽

2021 ◽

Vol 14 (9) ◽

pp. 873

Author(s):

Abanoub Riad ◽

Barbora Hocková ◽

Lucia Kantorová ◽

Rastislav Slávik ◽

Lucia Spurná ◽

...

Keyword(s):

Side Effects ◽

Side Effect ◽

Healthcare Workers ◽

Large Scale ◽

Large Population ◽

Medical Attention ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Post Vaccination ◽

Phase Iv

mRNA-based COVID-19 vaccines such as BNT162b2 have recently been a target of anti-vaccination campaigns due to their novelty in the healthcare industry; nevertheless, these vaccines have exhibited excellent results in terms of efficacy and safety. As a consequence, they acquired the first approvals from drug regulators and were deployed at a large scale among priority groups, including healthcare workers. This phase IV study was designed as a nationwide cross-sectional survey to evaluate the post-vaccination side effects among healthcare workers in Slovakia. The study used a validated self-administered questionnaire that inquired about participants’ demographic information, medical anamneses, COVID-19-related anamnesis, and local, systemic, oral, and skin-related side effects following receiving the BNT162b2 vaccine. A total of 522 participants were included in this study, of whom 77% were females, 55.7% were aged between 31 and 54 years, and 41.6% were from Banska Bystrica. Most of the participants (91.6%) reported at least one side effect. Injection site pain (85.2%) was the most common local side effect, while fatigue (54.2%), headache (34.3%), muscle pain (28.4%), and chills (26.4%) were the most common systemic side effects. The reported side effects were of a mild nature (99.6%) that did not require medical attention and a short duration, as most of them (90.4%) were resolved within three days. Females and young adults were more likely to report post-vaccination side effects; such a finding is also consistent with what was previously reported by other phase IV studies worldwide. The role of chronic illnesses and medical treatments in post-vaccination side effect incidence and intensity requires further robust investigation among large population groups.

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BERTMeSH: deep contextual representation learning for large-scale high-performance MeSH indexing with full text

Bioinformatics ◽

10.1093/bioinformatics/btaa837 ◽

2020 ◽

Author(s):

Ronghui You ◽

Yuxuan Liu ◽

Hiroshi Mamitsuka ◽

Shanfeng Zhu

Keyword(s):

Full Text ◽

High Performance ◽

Large Scale ◽

Learning Strategy ◽

Learning To Rank ◽

Representation Learning ◽

Supplementary Information ◽

Medical Subject Headings ◽

The Difference ◽

Contextual Representation

Abstract Motivation With the rapid increase of biomedical articles, large-scale automatic Medical Subject Headings (MeSH) indexing has become increasingly important. FullMeSH, the only method for large-scale MeSH indexing with full text, suffers from three major drawbacks: FullMeSH (i) uses Learning To Rank, which is time-consuming, (ii) can capture some pre-defined sections only in full text and (iii) ignores the whole MEDLINE database. Results We propose a computationally lighter, full text and deep-learning-based MeSH indexing method, BERTMeSH, which is flexible for section organization in full text. BERTMeSH has two technologies: (i) the state-of-the-art pre-trained deep contextual representation, Bidirectional Encoder Representations from Transformers (BERT), which makes BERTMeSH capture deep semantics of full text. (ii) A transfer learning strategy for using both full text in PubMed Central (PMC) and title and abstract (only and no full text) in MEDLINE, to take advantages of both. In our experiments, BERTMeSH was pre-trained with 3 million MEDLINE citations and trained on ∼1.5 million full texts in PMC. BERTMeSH outperformed various cutting-edge baselines. For example, for 20 K test articles of PMC, BERTMeSH achieved a Micro F-measure of 69.2%, which was 6.3% higher than FullMeSH with the difference being statistically significant. Also prediction of 20 K test articles needed 5 min by BERTMeSH, while it took more than 10 h by FullMeSH, proving the computational efficiency of BERTMeSH. Supplementary information Supplementary data are available at Bioinformatics online

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Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin

Biomolecules ◽

10.3390/biom10121640 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1640

Author(s):

Tomáš Zimmermann ◽

Pavel Drašar ◽

Silvie Rimpelová ◽

Søren Brøgger Christensen ◽

Vladimir A. Khripach ◽

...

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Sesquiterpene Lactone ◽

Large Scale ◽

Active Principle ◽

Chemotherapeutic Drug ◽

Limited Access ◽

General Toxicity ◽

Clinical Potential

In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.

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