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Journal of Controlled Release :... Jun 2024Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant...
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8NKG2DT cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.
PubMed: 38936744
DOI: 10.1016/j.jconrel.2024.06.060 -
Gynecologic Oncology Jun 2024Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic... (Review)
Review
BACKGROUND
Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic cancers. Scalp hypothermia, also known as "cold caps", is a possible method to prevent severe CIA, studied primarily in the breast cancer population.
OBJECTIVES
To compile existing data on scalp hypothermia in cancer patients receiving taxane chemotherapy in order to investigate its application to the gynecologic cancer population.
SEARCH STRATEGY
MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and Cochrane were searched through January 31, 2023.
SELECTION CRITERIA
Full-text manuscripts reporting on the results of scalp hypothermia in patients receiving taxane-based chemotherapy.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1424 records, we included 31 studies, representing 14 different countries. Only 5 studies included gynecologic cancer patients. We extracted the outcome of the proportion of patients with <50% hair loss. Among 2179 included patients, 60.7% were reported to have <50% hair loss (meta-analysis: 60.6%, 95% confidence interval [CI] 54.9-66.1%). Among the 28 studies reporting only on taxane-based chemotherapy, the rate of <50% hair loss was 60.0% (meta-analysis: 60.9%, (95% CI: 54.9-66.7%). In comparative studies, hair loss was significantly less in patients who received scalp hypothermia versus those who did not (49.3% versus 0% with <50% hair loss; OR 40.3, 95% CI: 10.5-154.8). Scalp cooling achieved <50% hair loss in patients receiving paclitaxel (67.7%; meta-analysis 69.9%, 95% CI 64.1-75.4%) and docetaxel (57.1%; meta-analysis 60.5%, 95% CI 50.0-71.6%). Meta-analysis on patient satisfaction in regard to scalp cooling found a satisfaction rate of 78.9% (95% CI 69.1-87.4%).
CONCLUSION
Scalp hypothermia may be an effective method to reduce some cases of CIA due to taxane chemotherapy, especially paclitaxel. More trials need to be done to determine the precise effects of scalp hypothermia in gynecologic cancer patients.
PubMed: 38936283
DOI: 10.1016/j.ygyno.2024.06.012 -
International Journal of Surgery... Jun 2024Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant...
BACKGROUND
Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC.
MATERIALS AND METHODS
Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed.
RESULTS
Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively.
CONCLUSIONS
The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.
PubMed: 38935124
DOI: 10.1097/JS9.0000000000001891 -
Dermatology (Basel, Switzerland) Jun 2024Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding...
INTRODUCTION
Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients' experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction.
METHODS
In the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients' satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The pre-specified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post-hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at Weeks 24 and 48.
RESULTS
At Week 24, the proportion of patients (N=718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group vs 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at Week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at Week 48 than at Week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at Weeks 24 (range 0.73-0.76; P<0.05) and 48 (0.74-0.77; P<0.05).
CONCLUSIONS
Patients receiving active ritlecitinib doses reported favorable results vs placebo in satisfaction with hair growth up to Week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction.
TRIAL REGISTRATION
Clinicaltrials.gov NCT0373280.
PubMed: 38934147
DOI: 10.1159/000539536 -
Cytotechnology Aug 2024A previous study indicated that patients with androgenic alopecia (AGA) have significantly reduced levels of . This study investigates whether promotes hair-follicle...
UNLABELLED
A previous study indicated that patients with androgenic alopecia (AGA) have significantly reduced levels of . This study investigates whether promotes hair-follicle recovery and its possible mechanism. Hair alteration and cutaneous histopathological changes induced by testosterone propionate were observed by H&E and bromodeoxyuridinc (BrdU) stain to evaluate the therapeutic effect of in C57BL/6 J mice. The cellular viability was analyzed in -transfected human hair-follicle stem cells (HFSCs) in vitro. The signaling pathways and pro-proliferative factors were investigated by transcriptomic gene sequencing and qRT-PCR. transfection successfully recovered hair growth and hair-follicle cells in AGA mice. In a series of HFSC studies in vitro, transfection greatly promoted cellular proliferation and decreased cellular apoptosis. Transcriptome gene sequencing suggested that the phosphatidylinositol 3-kinase (PI3K)-Akt pathway was upregulated by . The qRT-PCR results showed that fibroblast growth factor (FGF)-2 was 14-times upregulated after transfection. Hair-follicle recovery activity of may involve the upregulation of and PI3K-Akt to promote follicle stem cell survival. These data not only provide a theoretical basis for AGA development but also reveal a novel therapeutic method for AGA patients.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10616-024-00624-3.
PubMed: 38933868
DOI: 10.1007/s10616-024-00624-3 -
Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Journal of Cosmetic Dermatology Jun 2024To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA).
OBJECTIVE
To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA).
METHODS
A case control study and two observational experiments on mice were conducted. In the first part, a total of 528 Chinese AGA patients and 500 age-matched healthy controls were included. Serum HCY levels of AGA and controls were compared. In the second part, eight mice were divided into two groups. Both groups of mice had their hair removed. AGA group received a DHT injection, and the other as control group. HCY levels in hair follicles (HFs) were detected by ELISA and compared. In the third part, twelve mice were divided into three groups and fed with different concentrations of methionine. After 4 weeks, serum HCY levels, parameters related to hair growth through observation and HE staining, and expression of immunohistochemistry (IHC) hair-growth-related markers Ki67, VEGF, IGF-1, Krt27, FGF9, and TGF-β1 were compared among the three groups.
RESULTS
In the first part, HCY levels were higher in AGA than the controls of both genders. However, there was no difference in HCY levels between groups with varying severity. Rates of hyperhomocysteinemia was higher in AGA patients than the controls. Logistic regression analysis showed serum HCY levels was positively correlated with the incidence of AGA. In the second part, HCY of the HFs in the AGA group was significantly higher than that in the control group. The third part showed that the increase in serum HCY levels inhibited the growth of mice hair, with the less expressed stimulative markers Ki67, VEGF, IGF-1, Krt27, and FGF9, while there was no difference in the expression of inhibitory markers TGF-β1.
CONCLUSION
There is a potential relationship between HCY and AGA. HCY had an inhibitory effect on hair growth. Further studies are necessary to explore the specific mechanism.
PubMed: 38932477
DOI: 10.1111/jocd.16440 -
Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study.Skin Research and Technology : Official... Jul 2024The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject.
PURPOSE
The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject.
DESIGN
Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method.
METHODS
In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids.
RESULTS
In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002).
CONCLUSION
This study found that serum lipids may be causally implicated in AA.
Topics: Alopecia Areata; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Lipids; Genetic Predisposition to Disease
PubMed: 38932455
DOI: 10.1111/srt.13785 -
Pharmaceutics Jun 2024This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral... (Review)
Review
This comprehensive review consolidates insights from two sources to emphasize the transformative impact of scaffold-based drug delivery systems in revolutionizing oral cancer therapy. By focusing on their core abilities to facilitate targeted and localized drug administration, these systems enhance therapeutic outcomes significantly. Scaffolds, notably those coated with anti-cancer agents such as cisplatin and paclitaxel, have proven effective in inhibiting oral cancer cell proliferation, establishing a promising avenue for site-specific drug delivery. The application of synthetic scaffolds, including Poly Ethylene Glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA), and natural materials, like collagen or silk, in 3D systems has been pivotal for controlled release of therapeutic agents, executing diverse anti-cancer strategies. A key advancement in this field is the advent of smart scaffolds designed for sequential cancer therapy, which strive to refine drug delivery systems, minimizing surgical interventions, accentuating the significance of 3D scaffolds in oral cancer management. These systems, encompassing local drug-coated scaffolds and other scaffold-based platforms, hold the potential to transform oral cancer treatment through precise interventions, yielding improved patient outcomes. Local drug delivery via scaffolds can mitigate systemic side effects typically associated with chemotherapy, such as nausea, alopecia, infections, and gastrointestinal issues. Post-drug release, scaffolds foster a conducive environment for non-cancerous cell growth, adhering and proliferation, demonstrating restorative potential. Strategies for controlled and targeted drug delivery in oral cancer therapy span injectable self-assembling peptide hydrogels, nanocarriers, and dual drug-loaded nanofibrous scaffolds. These systems ensure prolonged release, synergistic effects, and tunable targeting, enhancing drug delivery efficiency while reducing systemic exposure. Smart scaffolds, capable of sequential drug release, transitioning to cell-friendly surfaces, and enabling combinatorial therapy, hold the promise to revolutionize treatment by delivering precise interventions and optimized outcomes. In essence, scaffold-based drug delivery systems, through their varied forms and functionalities, are reshaping oral cancer therapy. They target drug delivery efficiency, diminish side effects, and present avenues for personalization. Challenges like fabrication intricacy, biocompatibility, and scalability call for additional research. Nonetheless, the perspective on scaffold-based systems in oral cancer treatment is optimistic, as ongoing advancements aim to surmount current limitations and fully leverage their potential in cancer therapy.
PubMed: 38931923
DOI: 10.3390/pharmaceutics16060802 -
Molecules (Basel, Switzerland) Jun 2024Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like...
BACKGROUND
Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like flavonoids (POFs) may improve hair quality in AGA. This study examines POFs' effectiveness in treating AGA-affected hair and repairing UV-induced damage.
METHODS
Hair samples were analyzed using scanning electron microscopy (SEM) to examine surface characteristics, electron paramagnetic resonance (EPR) spectroscopy to measure free radicals in the hair, and spectrophotometry to assess changes in hair properties.
RESULTS
POFs effectively removed hydroxyl radicals from keratinocytes and had antioxidant properties. They also reduced UV-induced damage to AGA hair by mitigating the production of melanin free radicals. Following POF treatment, the reduction in peroxidized lipid loss in AGA hair was notable at 59.72%, thereby effectively delaying the progression of hair color change. Moreover, protein loss decreased by 191.1 μ/g and tryptophan loss by 15.03%, ultimately enhancing hair's tensile strength.
CONCLUSION
compared to healthy hair, hair damaged by AGA shows more pronounced signs of damage when exposed to UV radiation. POFs help protect balding hair by reducing oxidative damage and slowing down melanin degradation.
Topics: Alopecia; Ultraviolet Rays; Humans; Antioxidants; Hair; Flavonoids; Plant Extracts; Melanins; Keratinocytes
PubMed: 38930941
DOI: 10.3390/molecules29122876