Search Results (43)

We herein designed a 64-chamber laminar-flow microfluidic chip with independently addressable culture units capable of establishing spatially heterogeneous chemical environments to mimic tissue microenvironments. Stable chemical gradients were successfully generated within the chip through controlled laminar flow, allowing precise spatial modulation of cellular exposure. Using TNF-α as a model stimulus, we observed a clear time delay in NF-κB activation between cells directly exposed to the cytokine and those located on the medium-only side, confirming the establishment of spatially distinct chemical conditions. Notably, even cells not directly exposed to TNF-α eventually responded, indicating that molecular diffusion along the static solid–liquid interface serves as an effective delivery route for bioactive molecules. To further demonstrate the platform’s utility, we constructed a skin-mimetic co-culture model of HaCaT keratinocytes and human skin fibroblasts (HSFs) to assess the diffusion and cytotoxic effects of 5-fluorouracil (5-FU). The results revealed that fibroblasts provided protective effects against 5-FU-induced cytotoxicity, likely via paracrine signaling or direct cell–cell interactions. These findings highlight the platform’s capacity for probing not only spatial drug-delivery dynamics but also intercellular interactions under physiologically relevant conditions. This system offers a powerful and versatile tool for studying spatiotemporal signaling, drug screening, and topical therapeutic development. Full article

Erythema ab igne (EAI), also known as “hot water bottle rash” or “toasted skin syndrome”, is a benign cutaneous condition caused by chronic exposure to low-level infrared heat. It typically begins as transient erythema and evolves into a reticulated brown pigmentation with telangiectasias. A skin biopsy, ideally taken from the central area of the hyperpigmented lesion, is recommended to exclude differential diagnoses. Although usually benign, EAI has been associated with rare malignant transformations, supported only by low-level evidence. Elimination of the heat source is essential, and topical treatments such as hydroquinone or retinoids may be considered, while agents like 5-fluorouracil or imiquimod are reserved for dysplastic lesions. Women with endometriosis frequently use heating devices to alleviate dysmenorrhea and chronic pelvic pain. However, prolonged or inappropriate heat application can lead to chronic thermal injury, including EAI, and may delay medical consultation. While controlled trials confirm short-term analgesic efficacy of heat therapy, extrapolating these findings to unrestricted home use without standardized safety recommendations can be misleading. EAI illustrates the broader impact of chronic pain in endometriosis, linking cutaneous manifestations with neuroplastic alterations and psychiatric comorbidities. A nuanced approach combining patient education on safe use of heat, close dermatologic monitoring, and multidisciplinary pain management is warranted. Full article

Background: Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare, life-threatening mucocutaneous disorders often associated with severe ophthalmic complications. Ocular involvement occurs in 50–68% of cases and can result in permanent vision loss. Despite this, optimal management strategies remain unclear, and treatment practices vary widely. Methods: A systematic review was conducted in accordance with PRISMA guidelines and prospectively registered on PROSPERO (CRD420251022655). Medline, Embase, and CENTRAL were searched from 1998 to 2024 for English-language studies reporting treatment outcomes for ocular SJS/TEN. Results: A total of 194 studies encompassing 6698 treated eyes were included. Best-corrected visual acuity (BCVA) improved in 52.2% of eyes, epithelial regeneration occurred in 16.8%, and symptom relief was reported in 26.3%. Common treatments included topical therapy (n = 1424), mucosal grafts (n = 1220), contact lenses (n = 1134), amniotic membrane transplantation (AMT) (n = 889), systemic medical therapy (n = 524), and punctal occlusion (n = 456). Emerging therapies included TNF-alpha inhibitors, anti-VEGF agents, photodynamic therapy, and 5-fluorouracil. Conclusions: Disease-stage-specific therapy is crucial in ocular SJS/TEN. Acute interventions such as AMT may prevent long-term complications, while chronic care targets structural and tear-film abnormalities. Further prospective studies are needed to standardize care and optimize visual outcomes. Full article

Background/Objectives: Despite advances in diagnosis and treatment, colorectal cancer (CRC) remains one of the most prevalent and challenging malignancies worldwide. The dysregulation of microRNAs (miRNAs) has emerged as a critical factor in CRC onset, progression, and therapeutic resistance. This study aims to provide an overview of global research trends on miRNAs in CRC, (i) identifying the most studied miRNAs, (ii) exploring under-investigated areas, and (iii) highlighting emerging themes and potential future directions. Methods: To assess the evolution of the global miRNA–CRC research trends, we conducted a bibliometric analysis of 828 CRC–miRNA-focused articles published between 2008 and 2024, sourced from the Scopus database. Bibliometric mapping was performed using the R/Bibliometrix package and by leveraging a customized Python-based pipeline, which is useful for extracting and validating miRNA identifiers (miRNA IDs) based on the miRBase database. This miRNA ID-related approach enabled us to systematically identify the most frequently studied miRNAs over time while highlighting underexplored miRNA. Results: The analysis revealed a substantial and accelerating publication growth rate, delineating three major phases in CRC–miRNA research. China emerged as the leading contributor in terms of the publication volume. miR-21, miR-34a, and miR-195-5p were among the most frequently studied miRNAs, underscoring their relevance to CRC biology and therapy. Keyword and citation analyses identified key thematic areas, such as cell proliferation, epithelial–mesenchymal transition, and chemoresistance, especially to oxaliplatin and 5-fluorouracil. Emerging research frontiers included ferroptosis, ceRNA networks, and exosome-mediated miRNA transport. An analysis of the collaborations indicated strong intra-national collaborations, with room for expanding international research networks. Conclusions: This study provides an in-depth bibliometric landscape of the CRC-related miRNA research by highlighting influential studies and journals while identifying gaps and underexplored topics. These insights offer valuable guidance for future translational and clinical research on this topic. Full article

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance. Full article

Melanoma is a malignant skin cancer associated with high mortality rates and drug resistance, posing a significant threat to human health. The combination of chemotherapy and photodynamic therapy (PDT) represents a promising strategy to enhance antitumor efficacy through synergistic anti-cancer effects. Topical delivery of chemotherapeutic drugs and photosensitizers (PS) offers a non-invasive and safe way to treat melanoma. However, the effectiveness of these treatments is often hindered by challenges such as limited skin permeability and instability of the PS. In this study, transfersomes (TFS) were designed to facilitate transdermal delivery of the chemotherapeutic drug 5-Fluorouracil (5-FU) and the PS Imperatorin (IMP) for combined chemo-photodynamic therapy for melanoma. The cytotoxic and phototoxic effects of TFS-mediated PDT (TFS-UVA) were investigated in A375 cells and nude mice. The study also demonstrated that TFS-UVA generated intracellular ROS, induced G2/ M phase cell cycle arrest, and promoted cell apoptosis. In conclusion, this study indicated that 5-FU/ IMP-TFS serves as an effective transdermal therapeutic strategy for chemo-PDT in treating melanoma. Full article

In this study, a novel multifunctional biofilm was fabricated using a straightforward casting process. The biofilm comprised gelatin, chitosan, 5-fluorouracil (5-FU)-conjugated zinc oxide nanoparticles, and polyvinyl alcohol plasticized with glycerol. The 5-FU-conjugated nanoparticles were synthesized via a single-step co-precipitation process, offering a unique approach. Characterization confirmed successful drug conjugation, revealing bar-shaped nanoparticles with sizes ranging from 90 to 100 nm. Drug release kinetics followed the Korsmeyer–Peppas model, indicating controlled release behavior. Maximum swelling ratio studies of the gelatin–chitosan film showed pH-dependent characteristics, highlighting its versatility. Comprehensive analysis using SEM, FT-IR, Raman, and EDX spectra confirmed the presence of gelatin, chitosan, and 5-FU/ZnO nanoparticles within the biofilms. These biofilms exhibited non-cytotoxicity to human fibroblasts and significant anticancer activity against skin cancer cells, demonstrating their potential for biomedical applications. This versatility positions the 5-FU/ZnO-loaded sheets as promising candidates for localized topical patches in skin and oral cancer treatment, underscoring their practicality and adaptability for therapeutic applications. Full article

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit^® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm²) formulated with various chemical permeation enhancers. The patches containing Transcutol^® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm² and 82.56 ± 8.2 µg/cm², respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles. Full article

Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson–Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir–Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions’ undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson–Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented. Full article

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin treatment is effective in hypertrophic scars and warts, but intralesional 5-FU may also be considered since it is cheaper and less painful. Moreover, intralesional 5-FU and bleomycin injection is a viable option for premalignant lesions (i.e., actinic keratosis) and inoperable skin cancers. Both bleomycin and 5-FU have been applied as treatment adjuncts for vitiligo, with 5-FU showing a slightly better outcome. Both agents have a good safety profile, and no serious side effects have been reported following their use in the field of dermatology. Full article

This original article presents the findings of a comprehensive case series, shedding light on the efficacy of diverse treatment modalities for managing precancerous and cancerous skin lesions and their remarkable rejuvenation effects on the skin. A particular focus is placed on the promising outcomes achieved through the application of a combination treatment involving 5-Fluorouracil (5-FU) and salicylic acid, which demonstrates enduring and noteworthy results. Furthermore, alternative therapeutic approaches, including 5-FU monotherapy, Methyl aminolevulinate–photodynamic therapy (MAL-PDT), and the combination of Imiquimod therapy with MAL-PDT, exhibit substantial potential for patients seeking non-surgical solutions. These treatments manifest as valuable tools in improving skin texture and mitigating the effects of photodamage. Nevertheless, the intricate interplay between the chosen treatment, the extent of photodamage, and individual patient characteristics, with a particular emphasis on age, necessitates long-term follow-up to gauge treatment outcomes and the likelihood of lesion recurrence. Notably, these treatments are associated with a significant degree of inflammation, igniting curiosity regarding enhanced skin cellular turnover and the potential for a more youthful skin appearance. Our findings accentuate the promise of topical fluorouracil (5-FU) and photodynamic therapy (PDT) in combating photoaging among patients with actinic keratoses. However, a need for further in-depth research is evident to unravel the nuanced relationships between these treatments, the severity of photodamage, and the influence of patient-specific factors. Such comprehensive investigations are instrumental in optimizing patient care and outcomes, offering a holistic approach to managing photodamage within the context of actinic keratoses. This work, when combined with existing literature, provides valuable insights and serves as a catalyst for future research to fully unlock the potential of these treatments, ultimately enhancing the quality of patient care. Full article

The therapeutic effectiveness of the most widely used anticancer drug 5-fluorouracil (5-FU) is constrained by its high metabolism, short half-life, and rapid drug resistance after chemotherapy. Although various nanodrug delivery systems have been reported for skin cancer therapy, their retention, penetration and targeting are still a matter of concern. Hence, in the current study, a topical gel formulation that contains a metal-organic framework (zeolitic imidazole framework; ZIF-8) loaded with 5-FU and a surface modified with sonidegib (SDG; acting as a therapeutic agent as well as a targeting ligand) (5-FU@ZIF-8 MOFs) is developed against DMBA-UV-induced BCC skin cancer in rats. The MOFs were prepared using one-pot synthesis followed by post drug loading and SDG conjugation. The optimized MOFs were incorporated into hyaluronic acid-hydroxypropyl methyl cellulose gel and further subjected to characterization. Enhanced skin deposition of the 5-FU@ZIF-8-SDG MOFs was observed using ex vivo skin permeation studies. Confocal laser microscopy studies showed that 5-FU@ZIF-8-SDG MOFs permeated the skin via the transfollicular pathway. The 5-FU@ZIF-8-SDG MOFs showed stronger cell growth inhibition in A431 cells and good biocompatibility with HaCaT cells. Histopathological studies showed that the efficacy of the optimized MOF gels improved as the epithelial cells manifested modest hyperplasia, nuclear pleomorphism, and dyskeratosis. Additionally, immunohistochemistry and protein expression studies demonstrated the improved effectiveness of the 5-FU@ZIF-8-SDG MOFs, which displayed a considerable reduction in the expression of Bcl-2 protein. Overall, the developed MOF gels showed good potential for the targeted delivery of multifunctional MOFs in topical formulations for treating BCC cancer. Full article

The use of topical and intralesional immunotherapy in the treatment of cutaneous malignant neoplasia in sensitive areas such as the lips and eyelids is discussed. Surgery may not be feasible or may result in deformities in these areas, making alternative treatment options necessary. A narrative literature review was conducted using MEDLINE (PubMed) as the main literature database, collecting available evidence of experiences with various topical and intralesional therapies in the aforementioned anatomical locations, ranging from case reports to clinical trials. The clearance rates and potential adverse reactions of therapeutic options such as imiquimod 5%, 5-fluorouracil (5-FU), photodynamic therapy (PDT), ingenol mebutate (IM), diclofenac, intralesional methotrexate, and interferon are reviewed. Although limited by their heterogeneity and the scarcity of clinical trials, these studies point towards promising response rates and minimal adverse effects, making these treatments viable options in selected cases. Full article

5-Fluorouracil (5-FU), a BCS class III drug, has low oral bioavailability and is cytotoxic in nature causing severe systemic side effects when administered through the intravenous route. Topical drug delivery could potentially mitigate the systemic side-effects. Microemulsions (MEs) would be an apt solution due to enhanced partitioning of the drug to the skin. However, conventional methods for preparing MEs are inefficient since they are not continuous and are very tedious and time-consuming processes hence revealing the need for the development of continuous manufacturing technology. In our study, 5-FU MEs were prepared using a continuous manufacturing Twin Screw Process (TSP) and its efficiency in the treatment of skin cancer was evaluated. Water-in-oil MEs were prepared using isopropyl myristate as the oil phase and Aerosol OT and Tween 80 as the surfactants. The average particle size was observed to be 178 nm. Transmission electron microscopy was employed to confirm the size and shape of the MEs. FTIR study proved no physical or chemical interaction between the excipients and the drug. In vitro drug release using vertical diffusion cells and ex vivo skin permeation studies showed that the drug was released sustainably and permeated across the skin, respectively. In in vitro cytotoxicity studies, 5-FU MEs were accessed in HaCat and A431 cell lines to determine percentage cell viability and IC50. Skin irritation and histopathological examination implied that the 5-FU MEs did not cause any significant irritation to the skin. In vivo pharmacodynamics studies in rats suggested that the optimised formulation was effective in treating squamous cell carcinoma (SCC). Therefore, 5-FU MEs efficiently overcame the various drawbacks faced during oral and intravenous drug delivery. Also, TSP proved to be a technique that overcomes the various problems associated with the conventional methods of preparing MEs. Full article

Skin cancer is an overarching label used to classify a variety of cutaneous malignancies. Surgical excision procedures are the commonly used treatments for these lesions; however, the choice to perform operative intervention may be influenced by other factors. Established research and literature suggest that topical treatments limit the need for surgical intervention and its commonly associated adverse effects, including infection and scarring. In addition, the growing indications for the usage of topical therapies in BCC treatment, as well as their increased availability and therapeutic options, allow for their greater applicability in the dermatology clinic. Certain topical therapies have been highlighted in research, especially those targeting basal cell carcinoma (BCC) and actinic keratosis (AK). There is also a clear correlation between cost and treatment outcomes, considering BCC’s ever-growing prevalence and the proportion of excised lesions being reported as malignant. This review will discuss BCC and AK lesion criteria that result in the most successful outcomes using topical treatments, then highlight the various topical treatment options, and finally address their clinical significance moving forward. Full article