-
Dermatology (Basel, Switzerland) 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is...
BACKGROUND
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management.
METHODS
A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies.
RESULTS
Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia.
CONCLUSIONS
This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.
Topics: Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Canada; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Mycosis Fungoides; Retrospective Studies; Sezary Syndrome; Skin Neoplasms; Treatment Outcome; Young Adult
PubMed: 33429396
DOI: 10.1159/000512484 -
Medicina (Kaunas, Lithuania) Nov 2020: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is...
: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is unsatisfactory and challenging. Conventional systemic treatments may be beneficial; however, their possible side effects and possible transient efficacy is still a problem. We aimed to present the clinical course and effect of treatment with alitretinoin on patients with prurigo nodularis initially treated with conventional treatments like oral antihistamine, cyclosporine, and phototherapy. : all the patients had prurigo nodularis refractory to conventional treatment. Their medical records included demographic features, past medical history, duration of disease, and treatment modalities; and the clinical courses of the patients were reviewed for this retrospective study. We evaluated patient pruritus and skin lesions for the duration. : we present reports involving 10 patients with refractory prurigo. All the patients in our cases were treated with oral alitretinoin after previous treatments and reported the improvement of skin lesions and pruritus within 2 weeks to 3 months. : we suggest that oral alitretinoin may be an effective and well tolerated treatment option for patients with intractable prurigo. Further clinical studies are warranted to confirm the long-lasting efficacy and safety of alitretinoin for treating patients with prurigo.
Topics: Alitretinoin; Cyclosporine; Humans; Prurigo; Pruritus; Retrospective Studies
PubMed: 33182351
DOI: 10.3390/medicina56110599 -
European Journal of Immunology Jan 2021Calcitriol and 9-cis retinoic acid (9cRA) play a fundamental role in shaping the adaptive immune response by altering the Ig profile and the differentiation of B cells,...
Calcitriol and 9-cis retinoic acid (9cRA) play a fundamental role in shaping the adaptive immune response by altering the Ig profile and the differentiation of B cells, controlled by their corresponding nuclear receptors, VDR and RAR. Herein, after the establishment of a plasmablast differentiation culture, we investigated how both ligands modulate human naïve B cell differentiation and to which extent VDR/RXR and RAR/RXR signaling interferes. Calcitriol and 9cRA mediated activation of purified naïve B cells resulted in a strong differentiation of CD27 CD38 plasmablasts and antibody secretion. The significant IgA response was preceded by a strong induction of α-germline transcription (GLT). Induction of αGLT and consecutively IgA secretion driven by calcitriol is a novel observation and we show by magnetic chromatin IP that this was mediated by recruitment of the VDR to the TGF-β promoter thus inducing TGF-β expression. Finally, as revealed by transcriptomic profiling calcitriol and 9cRA modulate several signals required for differentiation and isotype switching in a noncompeting but rather additive manner. Calcitriol and 9cRA participate in the control of the IgA response in human activated naïve B cells. The balance between both ligands may be an important factor in channeling humoral immune responses toward a protective direction.
Topics: Adaptive Immunity; Alitretinoin; B-Lymphocytes; Binding Sites; CD40 Ligand; Calcitriol; Cell Differentiation; Cells, Cultured; GTP-Binding Proteins; Gene Expression; Humans; Immunoglobulin A; Immunoglobulin Class Switching; Interleukin-4; Ligands; Lymphocyte Activation; Plasma Cells; Promoter Regions, Genetic; Protein Glutamine gamma Glutamyltransferase 2; Receptors, Calcitriol; Receptors, Retinoic Acid; Retinoid X Receptors; Signal Transduction; Transforming Growth Factor beta1; Transglutaminases; Vitamin D3 24-Hydroxylase
PubMed: 33107588
DOI: 10.1002/eji.202048557 -
Chemical Communications (Cambridge,... Jul 2020Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)IFN) is loaded...
Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)IFN) is loaded with 9-cis-retinoic acid and capped with interferon-γ, whereas the second community of nanoparticles (i.e.S(sulf)PIC) is loaded with sulforhodamine B and capped with poly(I:C). The uptake of S(RA)IFN by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake of S(sulf)PIC and cell killing.
Topics: Alitretinoin; Antineoplastic Agents; Apoptosis; Cell Communication; Cell Line, Tumor; Gene Expression Regulation; Humans; Interferon Inducers; Interferon-gamma; Nanoparticles; Poly I-C; Rhodamines; Toll-Like Receptor 3
PubMed: 32478368
DOI: 10.1039/d0cc02795b -
Aging Mar 2020Alzheimer's disease (AD) is associated with the accumulation and deposition of a beta-amyloid (Αβ) peptide in the brain, resulting in increased neuroinflammation and...
Alzheimer's disease (AD) is associated with the accumulation and deposition of a beta-amyloid (Αβ) peptide in the brain, resulting in increased neuroinflammation and synaptic dysfunction. Intranasal delivery of targeted drugs to the brain represents a noninvasive pathway that bypasses the blood-brain barrier and minimizes systemic exposure. The aim of this study was to evaluate the therapeutic effect of intranasally delivered 9-cis retinoic acid (RA) on the neuropathology of an AD mouse model. Herein, we observed dramatically decreased Αβ deposition in the brains of amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice (APP/PS1) treated intranasally with 9-cis RA for 4 weeks compared to that in the brains of vehicle-treated mice. Importantly, intranasal delivery of 9-cis RA suppressed Αβ-associated astrocyte activation and neuroinflammation and ultimately restored synaptic deficits in APP/PS1 transgenic mice. These results support the critical roles of Αβ-associated neuroinflammation responses to synaptic deficits, particularly during the deposition of Αβ. Our findings provide strong evidence that intranasally delivered 9-cis RA attenuates neuronal dysfunction in an AD mouse model and is a promising therapeutic strategy for the prevention and treatment of AD.
Topics: Administration, Intranasal; Alitretinoin; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Astrocytes; Brain; Disease Models, Animal; Inflammation; Inflammation Mediators; Mice; Mice, Transgenic; Microglia; Presenilin-1
PubMed: 32209731
DOI: 10.18632/aging.102970 -
SAGE Open Medical Case Reports 2020Hailey-Hailey disease is an autosomal dominant genodermatosis leading to chronic hyperkeratotic and fissured lesions in the intertriginous areas. We present a...
Hailey-Hailey disease is an autosomal dominant genodermatosis leading to chronic hyperkeratotic and fissured lesions in the intertriginous areas. We present a 53-year-old woman with a case of vulvar and inguinal Hailey-Hailey disease resistant to usual treatments. She was efficiently treated with alitretinoin 10 mg daily combined with injections of onabotulinumtoxinA every 9 months. The combination led to an almost complete resolution of the lesions and symptoms at follow-ups.
PubMed: 32110406
DOI: 10.1177/2050313X20905678 -
The Cochrane Database of Systematic... Jan 2020Palmoplantar pustulosis is a chronic inflammatory disease in which sterile, relapsing pustules appear on the palms and soles, possibly in conjunction with other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Palmoplantar pustulosis is a chronic inflammatory disease in which sterile, relapsing pustules appear on the palms and soles, possibly in conjunction with other symptoms. The previous Cochrane Review on this topic was published in 2006, before biological treatments were extensively used.
OBJECTIVES
To assess the effects of interventions for chronic palmoplantar pustulosis to induce and maintain complete remission.
SEARCH METHODS
We searched the following databases up to March 2019: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of the included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
We considered RCTs including people with palmoplantar pustulosis or chronic palmoplantar pustular psoriasis assessing topical therapy, systemic therapy, combinations of topical or systemic therapies, or non-pharmacological therapies compared with placebo, no intervention, or each other.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our outcomes included 'Proportion of participants cleared or almost cleared', 'Proportion of participants with adverse effects serious or severe enough to cause withdrawal', 'Proportion of participants with at least 50% improvement in disease severity', and 'Proportion of participants with adverse effects'.
MAIN RESULTS
We included 37 studies (1663 participants; mean age 50 years (range 34 to 63); 24% males). These studies reported condition severity differently. Around half of the included trials stated the setting (hospitals, community clinics, or both). More than half of the studies were at high risk of bias in at least one domain. Our included studies assessed mainly systemic treatments (retinoids, ciclosporin, biologics, etretinate + PUVA (combination of psoralens and long-wave ultraviolet radiation) therapy combined, and antibiotics), but also topical treatments (dermocorticoids, vitamin D) and phototherapy (PUVA, ultraviolet A1 (UVA1)). Other interventions were assessed by single studies. The most common comparator was placebo. All results presented in this abstract were assessed in the short term (mean treatment duration was 11 weeks (range 8 to 24 weeks)) and are based on participants with chronic palmoplantar pustulosis. All outcome time point measurements were taken from baseline and assessed at the end of treatment. Short-term and long-term outcomes were defined as measurement up to 24 weeks after randomisation and between 24 and 104 weeks after randomisation, respectively. One trial (188 participants) assessed the topical vitamin D derivative maxacalcitol versus placebo and found that maxacalcitol may be more effective than placebo in achieving clearance (risk ratio (RR) 7.83, 95% confidence interval (CI) 1.85 to 33.12; low-quality evidence), and the risk of adverse effects (such as mild local irritation, pruritus, and haematological or urinary test abnormalities) is probably similar in both groups (RR 0.87, 95% CI 0.64 to 1.19; moderate-quality evidence). Severity was not reported. Two trials (49 participants) assessed PUVA therapy versus placebo or no treatment, providing very low-quality evidence. Adverse effects were reported with oral PUVA (including nausea, ankle swelling, and non-purulent conjunctivitis) and with local PUVA (including blistering, erythema, and pruritus). With regard to the systemic retinoid alitretinoin, one trial (33 participants; moderate-quality evidence) showed that alitretinoin probably makes little or no difference in reducing severity when compared to placebo (RR 0.69, 95% CI 0.36 to 1.30). A similar number of adverse events were reported in both treatment groups, including headache, cheilitis, nausea, arthralgia, and nasopharyngitis (RR 0.84, 95% CI 0.61 to 1.17). Clearance was not reported. There may be little or no difference between etanercept and placebo in achieving clearance (RR 1.64, 95% CI 0.08 to 34.28; 1 study; 15 participants; low-quality evidence); however, the 95% CI was very wide, showing there may be a difference between groups. Severity was not measured. More patients treated with placebo may achieve reduced severity than those treated with ustekinumab, but the wide 95% CI indicates there might be little or no difference between groups and there might be greater effect with ustekinumab (RR 0.48, 95% CI 0.11 to 2.13; 1 study; 33 participants; low-quality evidence). Clearance was not reported. It is uncertain whether guselkumab increases clearance when compared to placebo (2 studies; 154 participants) because the quality of evidence is very low, but guselkumab probably better reduces disease severity (RR 2.88, 95% CI 1.24 to 6.69; 1 study; 49 participants; moderate-quality evidence). Secukinumab is probably superior to placebo in reducing severity (RR 1.55, 95% CI 1.02 to 2.35; 1 study; 157 participants; moderate-quality evidence), but our clearance outcome was not reported. None of these trials reported on occurrence of adverse effects. Only two of the studies discussed above reported adverse effects serious or severe enough to cause withdrawal. Guselkumab may cause more serious adverse events when compared to placebo, but there is uncertainty due to the very wide 95% CI showing there may be little or no difference and showing more events with placebo (RR 2.88, 95% CI 0.32 to 25.80; 1 study; 49 participants; low-quality evidence). Secukinumab probably causes more serious adverse events than placebo (RR 3.29, 95% CI 1.40 to 7.75; 1 study; 157 participants; moderate-quality evidence).
AUTHORS' CONCLUSIONS
Evidence is lacking for major chronic palmoplantar pustulosis treatments such as superpotent corticosteroids, phototherapy, acitretin, methotrexate, and ciclosporin. Risk of bias and imprecision limit our confidence. Maxacalcitol may be more effective than placebo in achieving clearance in the short term (low-quality evidence), and the risk of adverse effects is probably similar (moderate-quality evidence). Oral alitretinoin is probably no more effective than placebo in reducing severity, with a similar risk of adverse effects (moderate-quality evidence). Regarding biological treatments, we are uncertain of the effect of etanercept on clearance and the effect of ustekinumab on severity (low-quality evidence). Secukinumab and guselkumab are probably superior to placebo in reducing severity (moderate-quality evidence). Adverse events not requiring withdrawal were not reported for these treatments. Reporting of serious adverse effects was incomplete: compared to placebo, secukinumab probably caused more participant withdrawals (moderate-quality evidence), but we are uncertain of the effect of guselkumab (low-quality evidence). Future trials should assess commonly used treatments using validated severity and quality of life scales.
Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Chronic Disease; Exanthema; Female; Humans; Male; Middle Aged; Phototherapy; Psoriasis; Quality of Life; Randomized Controlled Trials as Topic; Remission Induction; Ultraviolet Rays; Ustekinumab
PubMed: 31958161
DOI: 10.1002/14651858.CD011628.pub2 -
Cancer Letters Mar 2020Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote...
Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores. In vitro and in vivo experiments demonstrated that miR-191 overexpression promotes radiation survival, and contributes to a more aggressive phenotype. Retinoid X receptor alpha, RXRA, was discovered to be a novel target of miR-191, and knockdown recapitulated radioresistance. Furthermore, treatment of prostate cancer cells with the RXRA agonist 9-cis-retinoic acid restored radiosensitivity. Supporting this relationship, patients with high miR-191 and low RXRA abundance experienced quicker biochemical recurrence. Reduced RXRA translated to a higher risk of distant failure after radiotherapy. Notably, this miR-191/RXRA interaction was conserved in a novel primary cell line derived from radiorecurrent prostate cancer. Together, our findings demonstrate that miR-191 promotes prostate cancer survival after radiotherapy, and highlights retinoids as a potential option to improve radiotherapy response.
Topics: Alitretinoin; Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Kallikreins; Kaplan-Meier Estimate; Male; Mice; MicroRNAs; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Primary Cell Culture; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Tolerance; Retinoid X Receptor alpha; Survival Rate; Time Factors; Xenograft Model Antitumor Assays
PubMed: 31874245
DOI: 10.1016/j.canlet.2019.12.025 -
Acta Dermato-venereologica Jan 2020
Topics: Administration, Oral; Alitretinoin; Chronic Disease; Cyclosporine; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Patient Safety; Retrospective Studies; Skin; Time Factors; Treatment Outcome
PubMed: 31821516
DOI: 10.2340/00015555-3392