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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 -
Frontiers in Bioscience (Landmark... Sep 2023Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours.
BACKGROUND
Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours.
METHODS
We studied a panel of putative CSC surface markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) in 40 established melanoma cell lines and four early-passage melanoma strains by flow cytometry. We additionally examined 40 formalin-fixed paraffin-embedded melanoma tissues using immunofluorescence microscopy. This was compared with their expression in healthy skin, normal differentiated melanocytes and fibroblasts.
RESULTS
Most of the putative CSC markers were expressed by both melanoma cell lines and tissues. When present, these proteins were expressed by the majority of cells in the population. However, the expression of these markers by cells in healthy skin sections, normal differentiated melanocytes, and fibroblasts revealed that differentiated non-malignant cells also expressed CSC markers indicating that they lack of specificity for CSCs. Culturing cell lines under conditions more characteristic of the tumour microenvironment upregulated CSC marker expressions in a proportion of cell lines, which correlated with improved cell growth and viability.
CONCLUSIONS
The testing of melanoma cell lines (n = 40), early-passage cell strains (n = 4), and melanoma tissues (n = 40) showed that several putative CSC markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) are commonly present in a large proportion of melanoma cells and . Further, we showed that these putative markers lack specificity for CSCs because they are also expressed in differentiated non-malignant cell types (melanocytes, fibroblasts, and skin), which could limit their use as therapeutic targets. These data are consistent with the emerging notion of CSC plasticity and phenotype switching within cancer cell populations.
Topics: Humans; Nestin; Biomarkers, Tumor; Antigens, CD; Melanoma; Cell Line, Tumor; Neoplastic Stem Cells; Adapalene; AC133 Antigen; Tumor Microenvironment
PubMed: 37796710
DOI: 10.31083/j.fbl2809193 -
Journal of the American Academy of... Nov 2023A three-pronged acne treatment approach-combining an antibiotic, antibacterial agent, and retinoid-may provide greater efficacy than single/double treatments. Topical...
BACKGROUND
A three-pronged acne treatment approach-combining an antibiotic, antibacterial agent, and retinoid-may provide greater efficacy than single/double treatments. Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (IDP-126) is the first fixed-dose triple-combination in development for acne.
OBJECTIVE
To confirm efficacy, safety, and tolerability of IDP-126 gel in acne treatment.
METHODS
Two phase 3, double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne (N = 183; N = 180) 2:1 to once-daily IDP-126 or vehicle gel. Co-primary endpoints comprised participants achieving ≥2-grade reduction from baseline in Evaluator's Global Severity Score (EGSS) and clear/almost clear skin (treatment success) and change from baseline in inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were assessed.
RESULTS
At week 12, 49.6% and 50.5% of participants achieved treatment success with IDP-126 versus 24.9% and 20.5% with vehicle (P < .01, both). IDP-126 also provided significantly greater reductions in inflammatory/noninflammatory lesions versus vehicle (least-squares mean percent range: 72.7% to 80.1% vs 47.6% to 59.6%; P < .001, all). Most TEAEs were of mild-moderate severity.
LIMITATIONS
Inter-observer bias/variation in acne severity ratings, limited treatment duration, and population differences that may not generalize to real-world populations.
CONCLUSION
The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in 2 clinical studies of participants with moderate-to-severe acne.
PubMed: 37656094
DOI: 10.1016/j.jaad.2022.08.069 -
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 -
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 -
Toxicon : Official Journal of the... Sep 2023Besides neuronal cells, botulinum neurotoxins (BoNTs) can also affect other cell types such as fibroblasts or keratinocytes. These cells play a key role in skin...
Besides neuronal cells, botulinum neurotoxins (BoNTs) can also affect other cell types such as fibroblasts or keratinocytes. These cells play a key role in skin conditions. Maintaining a high-quality sebum secretion is essential to avoid premature aging. This study explored the effect of abobotulinumtoxinA (aboBoNT-A) in the rhino mouse. Briefly, anaesthetized animals were injected via the intra-dermal route (ID; four sites of injection) by either vehicle or 0.1, 0.3 and 1 Unit aboBoNT-A per mouse. A reference group was administered with adapalene gel 0.1% (daily local application) for 15 days. Adapalene is a third-generation retinoid and is used as first-line treatment of moderate acne. The body weight and the thickness of the dorsal skin were measured on days 1, 5, 10 and 15; erythema and scaling were recorded at the same time. On day 15, animals were ethically euthanized and skin samples were collected for histology, ELISA and lipidomic assays. AboBoNT-A administered ID at the doses 0.1 U and 0.3 U per mouse was well tolerated. 1 U aboBoNT-A (per mouse) induced a transient loss of muscle tone associated with a slight body weight loss after which mice recovered a good health status. AboBoNT-A did not show any significant effect on utricles surface area but induced a significant anti-inflammatory effect on dermis at the two highest doses. Moreover, aboBoNT-A showed neither side effects commonly observed with local retinoids, nor hyperplasia or dermis inflammation. No change in skin Interleukin-1alpha (IL-1α) cytokine levels was evidenced with aboBoNT-A, whereas a dose-dependent increase of substance P (SP) concentration in the skin was recorded, suggesting that aboBoNT-A induces neuropeptide accumulation in tissue by inhibiting exocytosis mechanisms. Lipidomic analysis showed that aboBoNT-A significantly increased the sebum concentration of several lipid species, presenting skin protecting properties. Overall, these data suggest that ID aboBoNT-A has skin rejuvenation, anti-inflammatory and moisture-boosting properties.
Topics: Mice; Animals; Sebum; Skin; Botulinum Toxins, Type A; Retinoids; Adapalene
PubMed: 37517594
DOI: 10.1016/j.toxicon.2023.107230 -
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