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Drug and Therapeutics Bulletin Dec 2023Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to... (Review)
Review
Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to permanent scars or pigment changes. Guidelines unanimously advise topical treatments as first-line, although differ in recommending either topical benzoyl peroxide or topical retinoid (mainly adapalene) alone or in combination. Guidance published by the National Institute for Health and Care Excellence advises counselling patients regarding avoidance of skin irritation when starting topical treatments and promoting adherence (treatments take 6-8 weeks to work). Oral antibiotics are currently overprescribed for acne but have a role when coprescribed with a non-antibiotic topical treatment. Hormonal treatments, such as the combined contraceptive pill, are also effective and there is growing evidence for the use of spironolactone for women with persistent acne. Recent guidance from the Medicines and Healthcare products Regulatory Agency regarding isotretinoin has implications for specialist prescribing and monitoring, and increasing public awareness of potential risks of mental health problems and sexual dysfunction. Although acne is associated with psychiatric disorder, the mental health effects of isotretinoin remain controversial.
Topics: Humans; Female; Isotretinoin; Acne Vulgaris; Benzoyl Peroxide; Anti-Bacterial Agents; Adapalene
PubMed: 38154809
DOI: 10.1136/dtb.2023.000051 -
Cancer Cell Apr 2024Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released...
Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify the retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound in prostate cancer (PCa). Reactivation of RARs triggers a robust senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of adapalene and docetaxel promotes a tumor-suppressive SASP that enhances natural killer (NK) cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of the allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in "immunologically cold" tumors.
Topics: Male; Humans; Animals; Mice; Cellular Senescence; Prostatic Neoplasms; Receptors, Retinoic Acid; Killer Cells, Natural; Adapalene
PubMed: 38428412
DOI: 10.1016/j.ccell.2024.02.004 -
Cutis Aug 2023A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness,... (Review)
Review
A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness, and costs. With the continued rise of dermatologic drug prices and increased cost-sharing due to high-deductible health plans, the importance of cost-effective treatment continues to grow. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. Combination topical products offer improved efficacy and convenience, which are associated with better adherence and outcomes. Generic fixed-dose adapalene-benzoyl peroxide (BPO) and fixed-dose clindamycin-BPO can be highly cost-effective options for patients with mild to moderate acne. Hormonal agents such as combined oral contraceptives (COCs) and spironolactone are inexpensive and likely reflect a highly cost-effective option that could reduce reliance on oral antibiotics in patients with moderate to severe acne. Doxycycline and isotretinoin also are cost-effective options for more severe acne. Frequent laboratory monitoring for spironolactone and isotretinoin continues to be prevalent despite little evidence to support its clinical utility, and it is associated with a major cost burden to the patient and health care system. The reduction of laboratory monitoring is an opportunity to provide higher-value care.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Isotretinoin; Adapalene; Cost-Benefit Analysis; Spironolactone; Drug Combinations; Acne Vulgaris; Treatment Outcome; Gels
PubMed: 37820334
DOI: 10.12788/cutis.0844 -
ACS Applied Bio Materials Sep 2023There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease,...
There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
Topics: Adult; Humans; Glioblastoma; Brain; Brain Neoplasms; Neural Stem Cells; Adapalene
PubMed: 37647213
DOI: 10.1021/acsabm.3c00447 -
The Journal of Dermatological Treatment Dec 2023Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel.
METHODS
Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne.
RESULTS
A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel.
CONCLUSIONS
The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.
Topics: Humans; Adolescent; Adult; Adapalene; Peroxides; Single-Blind Method; Benzoyl Peroxide; Acne Vulgaris
PubMed: 37341243
DOI: 10.1080/09546634.2023.2220446 -
The Journal of Dermatological Treatment Dec 2023Irritation with topical retinoids presents a significant impediment to acne treatment adherence. Two studies assessed the irritation potential of tazarotene 0.045%... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Irritation with topical retinoids presents a significant impediment to acne treatment adherence. Two studies assessed the irritation potential of tazarotene 0.045% lotion versus adapalene 0.3% gel and trifarotene 0.005% cream.
METHODS
In two double-blind, 12-day modified cumulative irritation patch studies, healthy adults (N = 20 each) had two active patches, containing 0.1 cc of tazarotene 0.045% lotion and either adapalene 0.3% gel (Study 1) or trifarotene 0.005% cream (Study 2), and one control patch (no product) placed on their upper back. Skin irritation was assessed and patches were replaced every 2-3 days.
RESULTS
In Study 1, tazarotene 0.045% lotion and adapalene 0.3% gel were both mildly irritating, though irritation was lower overall with tazarotene 0.045% lotion. In Study 2, significantly greater irritation was observed with trifarotene 0.005% cream than tazarotene 0.045% lotion, beginning two days after the first patch application and at each subsequent visit. In sub-analyses of data from both studies, irritation among participants with acne was similar to the overall study populations.
CONCLUSIONS
In two head-to-head studies comparing the irritation potential of third- and fourth-generation retinoids, tazarotene 0.045% lotion was significantly less irritating than trifarotene 0.005% cream and numerically less irritating than adapalene 0.3% gel.
Topics: Adult; Humans; Adapalene; Dermatologic Agents; Naphthalenes; Retinoids; Acne Vulgaris; Emollients; Double-Blind Method; Treatment Outcome
PubMed: 36622889
DOI: 10.1080/09546634.2023.2166346 -
Thoracic Cancer Mar 2024Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage...
BACKGROUND
Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR-TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder.
METHODS
To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF-α and IL-1β. We used qRT-PCR to analyze chemokine-induced inflammation and western blotting to analyze the effects of adapalene on the NF-κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT-PCR.
RESULTS
Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration-dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E-cadherin, were significantly downregulated by EGFR-TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib-induced phosphorylation of p65 was decreased by adapalene.
CONCLUSION
We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR-TKIs.
Topics: Humans; Animals; Mice; Afatinib; Erlotinib Hydrochloride; Adapalene; ErbB Receptors; Skin Diseases; Inflammation; Protein Kinase Inhibitors; Lung Neoplasms
PubMed: 38379420
DOI: 10.1111/1759-7714.15249 -
Cancers Aug 2023The majority of hematopoietic cancers in adults are incurable and exhibit unpredictable remitting-relapsing patterns in response to various therapies. The proto-oncogene...
The majority of hematopoietic cancers in adults are incurable and exhibit unpredictable remitting-relapsing patterns in response to various therapies. The proto-oncogene c-MYC has been associated with tumorigenesis, especially in hematological neoplasms. Therefore, targeting c-MYC is crucial to find effective, novel treatments for blood malignancies. To date, there are no clinically approved c-MYC inhibitors. In this study, we virtually screened 1578 Food and Drug Administration (FDA)-approved drugs from the ZINC15 database against c-MYC. The top 117 compounds from PyRx-based screening with the best binding affinities to c-MYC were subjected to molecular docking studies with AutoDock 4.2.6. Retinoids consist of synthetic and natural vitamin A derivatives. All-trans-retinoic acid (ATRA) were highly effective in hematological malignancies. In this study, adapalene, a third-generation retinoid usually used to treat acne vulgaris, was selected as a potent c-MYC inhibitor as it robustly bound to c-MYC with a lowest binding energy (LBE) of -7.27 kcal/mol, a predicted inhibition constant (pKi) of 4.69 µM, and a dissociation constant (K value) of 3.05 µM. Thus, we examined its impact on multiple myeloma (MM) cells in vitro and evaluated its efficiency in vivo using a xenograft tumor zebrafish model. We demonstrated that adapalene exerted substantial cytotoxicity against a panel of nine MM and two leukemic cell lines, with AMO1 cells being the most susceptible one (IC = 1.76 ± 0.39 µM) and, hence, the focus of this work. Adapalene (0.5 × IC, 1 × IC, 2 × IC) decreased c-MYC expression and transcriptional activity in AMO1 cells in a dose-dependent manner. An examination of the cell cycle revealed that adapalene halted the cells in the G/M phase and increased the portion of cells in the sub-G/G phase after 48 and 72 h, indicating that cells failed to initiate mitosis, and consequently, cell death was triggered. Adapalene also increased the number of p-H3(Ser10) positive AMO1 cells, which is a further proof of its ability to prevent mitotic exit. Confocal imaging demonstrated that adapalene destroyed the tubulin network of U2OS cells stably transfected with a cDNA coding for α-tubulin-GFP, refraining the migration of malignant cells. Furthermore, adapalene induced DNA damage in AMO1 cells. It also induced apoptosis and autophagy, as demonstrated by flow cytometry and western blotting. Finally, adapalene impeded tumor growth in a xenograft tumor zebrafish model. In summary, the discovery of the vitamin A derivative adapalene as a c-MYC inhibitor reveals its potential as an avant-garde treatment for MM.
PubMed: 37627164
DOI: 10.3390/cancers15164136