Nuclear Receptor and Stress Response Pathways Associated with Antineoplastic Agent-Induced Diarrhea

Okunaka, Mashiro; Kano, Daisuke; Uesawa, Yoshihiro

doi:10.3390/ijms232012407

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…The Toxicity Predictor can predict the agonist and antagonist activities of a drug in the MIE, which is the starting point of action of an adverse effect. Previous reports have described methods for evaluating the MIEs of adverse effects using Toxicity Predictor [ 13 ]. We believe that such methods are reliable [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous factors are involved in the mechanism of the effects of adverse drug reactions. From the perspective of toxicology, molecular initiating events (MIEs) in the adverse outcome pathway (AOP) represent an important concept when considering the mechanism of drug-induced adverse effects [ 13 ]. MIEs denote the first interaction between a molecule and a biomolecule or the biological system in the AOP.…”

Section: Introductionmentioning

confidence: 99%

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The Association between Molecular Initiating Events and Drug-Induced Hiccups

Hosoya,

Ishii-Nozawa,

Terajima

et al. 2024

Pharmaceuticals

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Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous reports have revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using the FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups was extracted from the overall population and sex-specific subgroups were divided. In each data table, the predicted activity values of nuclear receptors and stress response pathways for each drug were calculated using the Toxicity Predictor, a machine-learning model. Transforming growth factor-beta and antioxidant response elements were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups. The use of an adverse event database and the machine-learning model, Toxicity Predictor, may be useful for generating hypotheses for other adverse effects with unknown mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Association between Molecular Initiating Events and Drug-Induced Hiccups

Hosoya,

Ishii-Nozawa,

Terajima

et al. 2024

Pharmaceuticals

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“…A 2 × 2 contingency table for each drug and AFF was generated and assessed using reported odds ratios (RORs) and Fisher's exact p-values (Figure 3). The 2 × 2 contingency table was corrected by adding 0.5 to all cells, because the estimation is unstable if each cell is 0 or smaller (Haldane-Anscombe 1/2 correction) [53,54]. In this study, drugs with RORs of 1 or greater and Fisher's exact p-values of 0.05 or less were considered to be potentially associated with AFF.…”

Section: Risk Factors For Affsmentioning

confidence: 99%

Examination of Risk Factors and Expression Patterns of Atypical Femoral Fractures Using the Japanese Adverse Drug Event Report Database: A Retrospective Pharmacovigilance Study

et al. 2023

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Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients tended to have an increased risk of onset with long-term administration of these drugs. AFF developed earlier for osteoporosis patients taking long-term BPs and denosumab compared to cancer patients.

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Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure

Zhang,

Wang,

Yan

et al. 2023

Advanced Science

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Traditional Chinese medicine (TCM) is widely used in clinical practice, including skin and gastrointestinal diseases. Here, a potential TCM QY305 (T‐QY305) is reported that can modulate the recruitment of neutrophil in skin and colon tissue thus reducing cutaneous adverse reaction and diarrhea induced by epidermal growth factor receptor inhibitors (EGFRIs). On another hand, the T‐QY305 formula, through regulating neutrophil recruitment features would highlight the presence of N‐QY305, a subunit nanostructure contained in T‐QY305, and confirm its role as potentially being the biomaterial conferring to T‐QY305 its pharmacodynamic features. Here, the clinical records of two patients are analyzed expressing cutaneous adverse reaction and demonstrate positive effect of T‐QY305 on the simultaneous inhibition of both cutaneous adverse reaction and diarrhea in animal models. The satisfying results obtained from T‐QY305, lead to further process to the isolation of N‐QY305 from T‐QY305, in order to demonstrate that the potency of T‐QY305 originates from the nanostructure N‐QY305. Compared to T‐QY305, N‐QY305 exhibits higher potency upon reducing adverse reactions. The data represent a promising candidate for reducing cutaneous adverse reaction and diarrhea, meanwhile proposing a new strategy to highlight the presence of nanostructures being the “King” of Chinese medicine formula as the pharmacodynamic basis.

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Nuclear Receptor and Stress Response Pathways Associated with Antineoplastic Agent-Induced Diarrhea

Cited by 4 publications

References 40 publications

The Association between Molecular Initiating Events and Drug-Induced Hiccups

The Association between Molecular Initiating Events and Drug-Induced Hiccups

Examination of Risk Factors and Expression Patterns of Atypical Femoral Fractures Using the Japanese Adverse Drug Event Report Database: A Retrospective Pharmacovigilance Study

Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure

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