| 1. |
- Sokolov, Aleksandr V., et al.
(författare)
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Brain Cancer Drug Discovery : Clinical Trials, Drug Classes, Targets, and Combinatorial Therapies
- 2021
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Ingår i: Pharmacological Reviews. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0031-6997 .- 1521-0081. ; 73:4, s. 1-32
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Forskningsöversikt (refereegranskat)abstract
- Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials. gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. Significance Statement-This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.
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| 2. |
- Tarasov, Vladimir A., et al.
(författare)
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Designing answer selection tests in JavaScript
- 2000
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Ingår i: Proceedings of the Fifth Inter-Karelian Conference on Learning and Teaching Science and Mathematics in Secondary and Higher Education. - Joensuu : University of Joensuu. ; , s. 175-179
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Tarasov, Vladimir A., et al.
(författare)
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Designing tools for testing with open-ended questions using Java technology
- 2003
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Ingår i: Towards Meaningful Mathematics and Science Education. - Joensuu : University of Joensuu. - 9524582805 ; , s. 91-97
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents an approach to designing computerised assessment tools for testing with open-ended questions. Student answers are analysed by comparing them to the correct ones, which are constructed using keywords that are essential for the meaning of the answers. The developed tools were used within a course at the Karelian State Pedagogical University. Students preferred open-ended questions to multiple-choice questions. Applying Java technologies and component-based approaches, allowed us to create flexible tools that could be used with diverse computer platforms and integrated into a learning environment.
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| 4. |
- Tarasov, Vladimir A., et al.
(författare)
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Using XML and the IMS QTI standard for the development of assessment tools
- 2003
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Ingår i: Proceedings of the Sixth Inter-Karelian Conferene on Mathematics and Science Education in the North-East of Europe: History, Traditions, Contemporary Issues. - Joensuu : University of Joensuu. - 9524583372 ; , s. 312-317
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The paper deals with the issue of using the IMS Question and Test Interoperability standard for the development of assessment tools. This standard is based on XML (eXtensible Markup Language) and intended for description of tests at a structural level independent from the computer platform. According to this standard, questions and tests can be represented as plain text, which is marked-up with XML tags. The testing tool reads a test description in XML and parses it to translate into the format used internally in the system. This approach allows to create test descriptions that are highly interchangeable, readable, and reusable.
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| 5. |
- Nazarova, Victoria A., et al.
(författare)
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Treatment of ADHD : Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials
- 2022
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders having a high influence on social interactions. The number of approved treatments and clinical trials for ADHD have increased markedly during the recent decade. This analytical review provides a quantitative overview of the existing pharmacological and non-pharmacological methods of ADHD treatments investigated in clinical trials during 1999-2021. A total of 695 interventional trials were manually assessed from clinicaltrial.gov with the search term "ADHD", and trial data has been used for analysis. A clear majority of the studies investigated non-pharmacological therapies (similar to 80%), including many behavioral options, such as social skills training, sleep and physical activity interventions, meditation and hypnotherapy. Devices, complementary and other alternative methods of ADHD treatment are also gaining attention. The pharmacological group accounts for similar to 20% of all the studies. The most common drug classes include central nervous system stimulants (e.g., methylphenidate hydrochloride, lisdexamfetamine dimesylate, amphetamine sulfate, mixed amphetamine salts, a combination of dexmethylphenidate hydrochloride and serdexmethylphenidate chloride), selective noradrenaline reuptake inhibitors (atomoxetine, viloxazine), and alpha2 adrenergic receptor agonists (guanfacine hydrochloride, clonidine hydrochloride). Several studies investigated antidepressants (e.g., bupropion hydrochloride, vortioxetine), and atypical antipsychotics (e.g., quetiapine, aripiprazole) but these are yet not approved by the FDA for ADHD treatment. We discuss the quantitative trends in clinical trials and provide an overview of the new drug agents and non-pharmacological therapies, drug targets, and novel treatment options.
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| 6. |
- Zobdeh, Farzin, et al.
(författare)
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Pharmacogenetics and Pain Treatment with a Focus on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Antidepressants : A Systematic Review
- 2022
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:6
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Forskningsöversikt (refereegranskat)abstract
- Background: This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment. Methods: A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021. Results: Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/CYP2C9; (2) celecoxib/CYP2C9; (3) piroxicam/CYP2C8, CYP2C9; (4) diclofenac/CYP2C9, UGT2B7, CYP2C8, ABCC2; (5) meloxicam/CYP2C9; (6) aspirin/CYP2C9, SLCO1B1, and CHST2; (7) amitriptyline/CYP2D6 and CYP2C19; (8) imipramine/CYP2C19; (9) nortriptyline/CYP2C19, CYP2D6, ABCB1; and (10) escitalopram/HTR2C, CYP2C19, and CYP1A2. Conclusions: Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the CYP2C9 poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
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| 7. |
- Zobdeh, Farzin, et al.
(författare)
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The Epigenetics of Migraine
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:11
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Forskningsöversikt (refereegranskat)abstract
- Migraine is a complex neurological disorder and a major cause of disability. A wide range of different drug classes such as triptans, antidepressants, anticonvulsants, analgesics, and beta-blockers are used in acute and preventive migraine therapy. Despite a considerable progress in the development of novel and targeted therapeutic interventions during recent years, e.g., drugs that inhibit the calcitonin gene-related peptide (CGRP) pathway, therapy success rates are still unsatisfactory. The diversity of drug classes used in migraine therapy partly reflects the limited perception of migraine pathophysiology. Genetics seems to explain only to a minor extent the susceptibility and pathophysiological aspects of migraine. While the role of genetics in migraine has been extensively studied in the past, the interest in studying the role of gene regulatory mechanisms in migraine pathophysiology is recently evolving. A better understanding of the causes and consequences of migraine-associated epigenetic changes could help to better understand migraine risk, pathogenesis, development, course, diagnosis, and prognosis. Additionally, it could be a promising avenue to discover new therapeutic targets for migraine treatment and monitoring. In this review, we summarize the state of the art regarding epigenetic findings in relation to migraine pathogenesis and potential therapeutic targets, with a focus on DNA methylation, histone acetylation, and microRNA-dependent regulation. Several genes and their methylation patterns such as CALCA (migraine symptoms and age of migraine onset), RAMP1, NPTX2, and SH2D5 (migraine chronification) and microRNA molecules such as miR-34a-5p and miR-382-5p (treatment response) seem especially worthy of further study regarding their role in migraine pathogenesis, course, and therapy. Additionally, changes in genes including COMT, GIT2, ZNF234, and SOCS1 have been linked to migraine progression to medication overuse headache (MOH), and several microRNA molecules such as let-7a-5p, let-7b-5p, let-7f-5p, miR-155, miR-126, let-7g, hsa-miR-34a-5p, hsa-miR-375, miR-181a, let-7b, miR-22, and miR-155-5p have been implicated with migraine pathophysiology. Epigenetic changes could be a potential tool for a better understanding of migraine pathophysiology and the identification of new therapeutic possibilities. However, further studies with larger sample sizes are needed to verify these early findings and to be able to establish epigenetic targets as disease predictors or therapeutic targets.
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