scholarly journals Nanoparticles use for Delivering Ursolic Acid in Cancer Therapy: A Scoping Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Andang Miatmoko ◽  
Ester Adelia Mianing ◽  
Retno Sari ◽  
Esti Hendradi
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Ursolic Acid ◽  
Scoping Review ◽  
Water Solubility ◽  
Clinical Chemistry ◽  
Survival Rates ◽  
Pharmacokinetic Data ◽  
Literature Study ◽  
Anticancer Efficacy

Ursolic acid is a natural pentacyclic triterpenoid that exerts a potent anticancer effect. Furthermore, it is classified as a BCS class IV compound possessing low permeability and water solubility, consequently demonstrating limited bioavailability in addition to low therapeutic effectiveness. Nanoparticles are developed to modify the physical characteristics of drug and can often be produced in the range of 30–200 nm, providing highly effective cancer therapy due to the Enhanced Permeation and Retention (EPR) Effect. This study aims to provide a review of the efficacy and safety of various types of Ursolic Acid-loading nanoparticles within the setting of preclinical and clinical anticancer studies. This literature study used scoping review method, where the extracted data must comply with the journal inclusion criteria of within years of 2010–2020. The identification stage produced 237 suitable articles. Duplicate screening was then conducted followed by the initial selection of 18 articles that had been reviewed and extracted for data analysis. Based on this review, the use of nanoparticles can be seen to increase the anticancer efficacy of Ursolic Acid in terms of several parameters including pharmacokinetic data, survival rates and inhibition rates, as well as the absence of serious toxicity in preclinical and clinical trials in terms of several parameters including body weight, blood clinical chemistry, and organ histipathology. Based on this review, the use of nanoparticles has been able to increase the anticancer efficacy of Ursolic Acid, as well as show the absence of serious toxicity in preclinical and clinical trials. Evenmore, the liposome carrier provides development data that has reached the clinical trial phase I. The use of nanoparticle provides high potential for Ursolic Acid delivery in cancer therapy.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

The Use of Digital Clinical Trial Methods in the Evaluation of Digital Therapeutics: A Scoping Review (Preprint)

2019 ◽  
Author(s):  
Allison Hirsch ◽  
Mahip Grewal ◽  
Anthony James Martorell ◽  
Brian Michael Iacoviello
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Scoping Review ◽  
Digital Technologies ◽  
Good Clinical Practice ◽  
The United States ◽  
Clinical Trial Research ◽  
Digital Methods ◽  
Clinical Trial Methods

BACKGROUND Digital Therapeutics (DTx) provide evidence based therapeutic health interventions that have been clinically validated to deliver therapeutic outcomes, such that the software is the treatment. Digital methodologies are increasingly adopted to conduct clinical trials due to advantages they provide including increases in efficiency and decreases in trial costs. Digital therapeutics are digital by design and can leverage the potential of digital and remote clinical trial methods. OBJECTIVE The principal purpose of this scoping review is to review the literature to determine whether digital technologies are being used in DTx clinical research, which type are being used and whether publications are noting any advantages to their use. As DTx development is an emerging field there are likely gaps in the knowledge base regarding DTx and clinical trials, and the purpose of this review is to illuminate those gaps. A secondary purpose is to consider questions which emerged during the review process including whether fully remote digital clinical research is appropriate for all health conditions and whether digital clinical trial methods are inline with the principles of Good Clinical Practice. METHODS 1,326 records were identified by searching research databases and 1,227 reviewed at the full-article level in order to determine if they were appropriate for inclusion. Confirmation of clinical trial status, use of digital clinical research methods and digital therapeutic status as well as inclusion and exclusion criteria were applied in order to determine relevant articles. Digital methods employed in DTx research were extracted from each article and these data were synthesized in order to determine which digital methods are currently used in clinical trial research. RESULTS After applying our criteria for scoping review inclusion, 11 articles were identified. All articles used at least one form of digital clinical research methodology enabling an element of remote research. The most commonly used digital methods are those related to recruitment, enrollment and the assessment of outcomes. A small number of articles reported using other methods such as online compensation (n = 3), or digital reminders for participants (n = 5). The majority of digital therapeutics clinical research using digital methods is conducted in the United States and increasing number of articles using digital methods are published each year. CONCLUSIONS Digital methods are used in clinical trial research evaluating DTx, though not frequently as evidenced by the low proportion of articles included in this review. Fully remote clinical trial research is not yet the standard, more frequently authors are using partially remote methods. Additionally, there is tremendous variability in the level of detail describing digital methods within the literature. As digital technologies continue to advance and the clinical research DTx literature matures, digital methods which facilitate remote research may be used more frequently.

scholarly journals Rationalisations for women-only randomised controlled trials in conditions that affect both sexes: a scoping review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043370
Author(s):  
Ainsley Matthewson ◽  
Olena Bereznyakova ◽  
Brian Dewar ◽  
Alexandra Davis ◽  
Mark Fedyk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Scoping Review ◽  
Randomised Controlled Trials ◽  
Standard Of Care ◽  
Standards Of Care ◽  
Controlled Trials ◽  
Theory Approach ◽  
Reference Centre ◽  
Cochrane Database ◽  
Randomised Controlled

IntroductionWomen have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care.ObjectiveIn an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them.MethodologyThis scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher’s Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics.SignificanceThe scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials.Ethics and disseminationResearch ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

scholarly journals BIOM-60. BIOMARKER EVALUATION FOR IMIPRIDONE ONC206 REVEALS ClpP, ATF4, MYC, EGFR and HIF1 AS KEY PREDICTORS OF ANTI-CANCER EFFICACY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii14-ii15
Author(s):  
Sara Morrow ◽  
Mathew Garnett ◽  
Ultan McDermott ◽  
Cyril Benes ◽  
Joshua Allen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Strong Predictor ◽  
Predictive Biomarkers ◽  
Receptor Expression ◽  
Tumor Type ◽  
Anticancer Efficacy ◽  
Type Selection ◽  
Egfr Expression ◽  
Transport Chain ◽  
Biomarker Evaluation

Abstract ONC206 is a DRD2 antagonist and ClpP agonist that is a chemical derivative of ONC201, which is in Phase II clinical trials for H3 K27M-mutant glioma. We have previously reported that dopamine receptor expression correlates with ONC201 and ONC206 efficacy. Here, we evaluated additional predictive biomarkers for both agents in the GDSC panel using RNA-seq expression data. ClpP emerged as a strong predictor of efficacy for ONC206 (IC50: p = 1.83E-4, AUC: 9.92E-13). ClpP activation enhances degradation of its substrates, including electron transport chain members responsible for oxidative phosphorylation (OXPHOS). Imipridones activate the integrated stress response involving ATF4 and cause proteasomal degradation of c-myc, which also reduces OXPHOS. Accordingly, high ATF4 (IC50: p = 4.92E-5, AUC: p=2.84E-9) and elevated c-myc correlated with ONC206 efficacy (IC50: p = 6.42E-6, AUC: 3.31E-12). EGFR expression is inversely correlate with DRD2 expression in glioma and its activation is associated with glycolysis. Low EGFR expression correlated with increased ONC206 efficacy (IC50: p = 4.32E-7, AUC: p = 6.44E-20). Loss of HIF1 shunts cellular metabolism toward OXPHOS. Low HIF1 expression correlated with increased anticancer efficacy for ONC206 (IC50: p = 1.96E-3, AUC: p = 1.56E-11). Expression of each of the five markers was significantly different in cell lines that achieved an IC90 with ONC206 (~10%) versus those that did not. A similar analysis for ONC201 revealed that ClpP, MYC and EGFR are more predictive of efficacy relative to ATF4 and HIF1. Combinatorial biomarker analyses revealed MYC/EGFR as the most significant predictor of IC50 for both agents. ClpP/MYC and ClpP/HIF1 were the most significant predictors of AUC for ONC201 and ONC206, respectively. Ongoing studies are further investigating tumor type enrichment of biomarkers. Prediction of innate imipridone sensitivity using biomarkers identified in this study may guide patient and tumor type selection in clinical trials.

scholarly journals Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5632
Author(s):  
Mariam Elshiaty ◽  
Hannah Schindler ◽  
Petros Christopoulos
Keyword(s):  
Kinase Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Phase 1 ◽  
Survival Rates ◽  
Cell Receptor ◽  
Therapeutic Success ◽  
Cell Lung Carcinoma ◽  
Anticancer Efficacy ◽  
Cell Therapies ◽  
Recent Phase

Building upon the resounding therapeutic success of monoclonal antibodies, and supported by accelerating progress in engineering methods, the field of multispecific therapeutic antibodies is growing rapidly. Over 140 different molecules are currently in clinical testing, with excellent results in recent phase 1–3 clinical trials for several of them. Multivalent bispecific IgG-modified formats predominate today, with a clear tendency for more target antigens and further increased valency in newer constructs. The strategies to augment anticancer efficacy are currently equally divided between disruption of multiple surface antigens, and additional redirection of cytotoxic T or NK lymphocytes against the tumor. Both effects complement other modern modalities, such as tyrosine kinase inhibitors and adoptive cell therapies, with which multispecifics are increasingly applied in combination or merged, for example, in the form of antibody producing CAR-T cells and oncolytics. While mainly focused on B-cell malignancies early on, the contemporary multispecific antibody sector accommodates twice as many trials against solid compared to hematologic cancers. An exciting emerging prospect is the targeting of intracellular neoantigens using T-cell receptor (TCR) fusion proteins or TCR-mimic antibody fragments. Considering the fact that introduction of PD-(L)1 inhibitors only a few years ago has already facilitated 5-year survival rates of 30–50% for per se highly lethal neoplasms, such as metastatic melanoma and non-small-cell lung carcinoma, the upcoming enforcement of current treatments with “next-generation” immunotherapeutics, offers a justified hope for the cure of some advanced cancers in the near future.

scholarly journals Sexual health and COVID-19: protocol for a scoping review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Navin Kumar ◽  
Kamila Janmohamed ◽  
Kate Nyhan ◽  
Laura Forastiere ◽  
Wei-Hong Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Sexual Health ◽  
Scoping Review ◽  
Current Knowledge ◽  
Grey Literature ◽  
Well Being ◽  
World Health ◽  
Original Research ◽  
Scoping Reviews

Abstract Background Global responses to the COVID-19 pandemic have exposed and exacerbated existing socioeconomic and health inequities that disproportionately affect the sexual health and well-being of many populations, including people of color, ethnic minority groups, women, and sexual and gender minority populations. Although there have been several reviews published on COVID-19 and health disparities across various populations, none has focused on sexual health. We plan to conduct a scoping review that seeks to fill several of the gaps in the current knowledge of sexual health in the COVID-19 era. Methods A scoping review focusing on sexual health and COVID-19 will be conducted. We will search (from January 2020 onwards) CINAHL, Africa-Wide Information, Web of Science Core Collection, Embase, Gender Studies Database, Gender Watch, Global Health, WHO Global Literature on Coronavirus Disease Database, WHO Global Index Medicus, PsycINFO, MEDLINE, and Sociological Abstracts. Grey literature will be identified using Disaster Lit, Google Scholar, governmental websites, and clinical trials registries (e.g., ClinicalTrial.gov, World Health Organization, International Clinical Trials Registry Platform, and International Standard Randomized Controlled Trial Number Registry). Study selection will conform to the Joanna Briggs Institute Reviewers’ Manual 2015 Methodology for JBI Scoping Reviews. Only English language, original studies will be considered for inclusion. Two reviewers will independently screen all citations, full-text articles, and abstract data. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods. Discussion Original research is urgently needed to mitigate the risks of COVID-19 on sexual health. The planned scoping review will help to address this gap. Systematic review registrations Systematic Review Registration: Open Science Framework osf/io/PRX8E

scholarly journals The use of FDI criteria in clinical trials on direct dental restorations: A scoping review

2018 ◽  
Vol 68 ◽  
pp. 1-9 ◽  
Author(s):  
Thomas Marquillier ◽  
Sophie Doméjean ◽  
Justine Le Clerc ◽  
Florence Chemla ◽  
Kerstin Gritsch ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Scoping Review ◽  
Dental Restorations

scholarly journals Radioprotective Effect of Hesperidin: A Systematic Review

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 370 ◽  
Author(s):  
Musa ◽  
Omyan ◽  
Esmaely ◽  
Shabeeb
Keyword(s):  
Clinical Trials ◽  
Survival Rates ◽  
Control Design ◽  
Case Control ◽  
Radioprotective Effect ◽  
Cellular Damage ◽  
Animal Cells ◽  
Meta Analyses ◽  
Late Side ◽  
Radioprotective Agent

Background and objectives: Ionizing radiation (IR) has been of immense benefit to man, especially for medical purposes (diagnostic imaging and radiotherapy). However, the risks of toxicity in healthy normal cells, leading to cellular damage as well as early and late side effects, have been major drawbacks. The aim of this study was to evaluate the radioprotective effect of hesperidin against IR-induced damage. Materials and Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were applied in reporting this study. A search was conducted using the electronic databases PubMed, Scopus, Embase, Google Scholar, and www.ClinicalTrials.gov for information about completed or ongoing clinical trials. Results: From our search results, 24 studies involving rats, mice, and cultured human and animal cells were included. An experimental case—control design was used in all studies. The studies showed that the administration of hesperidin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, it increased 30-day and 60-day survival rates and protected against DNA damage. The best radioprotection was obtained when hesperidin was administered before irradiation. Conclusions: The results of the included studies support the antioxidant, anti-inflammatory, and antiapoptotic abilities of hesperidin as a potential radioprotective agent against IR-induced damage. We recommend future clinical trials for more insights.

EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi91-vi91
Author(s):  
Yeonju Kim ◽  
Terri Armstrong ◽  
Mark Gilbert ◽  
Orieta Celiku
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Tumor ◽  
Objective Response ◽  
Survival Rates ◽  
Maximum Tolerated Dose ◽  
Secondary Outcome ◽  
Patient Reported

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.

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