Precancerous Skin Research Articles

Tirbanibulin: A New Topical Therapy for Actinic Keratoses With a Novel Mechanism of Action and Improved Ease of Use.

Tirbanibulin: A New Topical Therapy for Actinic Keratoses With a Novel Mechanism of Action and Improved Ease of Use.

Innate Lymphoid Cells: New Targets for Cutaneous Squamous Cell Carcinoma Immunotherapy

The importance of innate immune cells in cancer promotion has been long recognized. Luci etal. (2021) show a key role for innate lymphoid cells (ILCs) in controlling precancerous skin lesions and impaired function of NK cells and ILC1s during progression to cutaneous squamous cell carcinoma (cSCC). These results, together with other findings, suggest that activation of ILCs could serve as a novel immunotherapeutic strategy against cSCC.

Efficacy and safety of hydrogen peroxide topical solution in treating actinic keratosis: A randomized controlled trial.

Actinic keratosis (AK) is a precancerous skin lesion associated with the development of squamous cell carcinoma. Approved topical treatments for AK are unmet needs. To evaluate the safety and efficacy of hydrogen peroxide topical solution 35% (H2 O2 ) with cryosurgery for the treatment of AKs. Eligible subjects were randomly assigned to receive H2 O2 and cryosurgery on each side of their scalp/face. Patients were assessed at baseline and after 3months of follow-up. Efficacy was evaluated based on the Actinic Keratosis Area and Severity Index (AKASI) and dermoscopic assessments. Fifteen patients with 98 lesions completed the study. At the follow-up visit, the mean improvement of AKASI from baseline was 1.7 ± 0.9 for H2 O2 and 1.7 ± 0.8 for cryosurgery (p < 0.001, both). Both treatments significantly improved dermoscopic features of yellow scale, white scale, linear-wavy vessels, pigmented dots, and rosette at the end of the 3-month follow-up. Complete dermoscopic response occurred in 57.7% and 73.9% of lesions treated with H2 O2 and cryosurgery, respectively (p > 0.05). Regarding safety, hypopigmentation occurred more frequently in the cryosurgery group (28.3% vs. 9.6%; p=0.017). Moreover, patients endured more pain with cryosurgery application than H2 O2 (p < 0.001). The effect of H2 O2 solution was comparable to cryosurgery. This treatment was well tolerated and had a favorable safety in patients with AKs.

Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies

Photodynamic therapy is one of the more unique cancer treatment options available in today’s arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers’ transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.

Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) inhibits cutaneous squamous cell carcinoma cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway

We previously demonstrated that M-PDT is painless and effective in precancerous skin diseases treatment. However, whether M-PDT is effective in cSCC and the underlying inhibitory mechanism remains enigmatic. We aims to unveil the effect of M-PDT on cSCC cell proliferation and the regulatory effect of M-PDT on MAPK signaling. The proliferation and migration of cSCC cells were revealed by CCK8 assay, tumor sphere formation assay and scratch assay respectively. The expression of MAPKs was examined by western blot. The activity of PP2A and PP5 was regulated by inhibitor and recombinant adenoviruses. Here, we show that M-PDT inhibits cSCC cell proliferation by activating p-JNK, p-p38 and inhibiting p-Erk1/2, as well as activation of PP2A and inactivation of PP5. Furthermore, pharmacological inhibition of PP2A conferred resistance to M-PDT's suppression on p-Erk1/2 and attenuated inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP2A showed the contrary results. Pharmacological inhibition of PP5 potentiated M-PDT's elevation on p-JNK and strengthened inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP5 exhibited the contrary results. Our findings indicate that M-PDT inhibits cSCC cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway.

Biodistribution and pharmacokinetic studies on topically delivered technetium-99m-labeled 5-FU nanogel formulation for management of pre-cancerous skin lesions

Purpose: To prepare technetium-99m (99mTc)-labelled nanogel loaded with 5-fluorouracil (5-FU) containing synthesized gallic acid-stearylamine (GA-SA) conjugate in order to reduce its systemic toxicity and provide site-specific delivery to skin lesions.&#x0D; Methods: Lipid nanocarrier-based 1 % (w/w) 5-FU nanogel containing GA-SA conjugate was successfully formulated. Parameters that included pH, viscosity and entrapment efficiency were measured. Furthermore, 1 % (w/w) 5-FU nanogel and 1 % (w/w) 5-FU commercial formulations were radiolabelled with 99mTc. The radiolabelled 99mTc-5-FU nanogel and commercial formulations were subjected to successive preclinical assessments with respect to radiochemical stability, biodistribution, and gamma scintigraphy in BALB/c mice, and pharmacokinetic studies in New Zealand albino rabbits.&#x0D; Results: The entrapment efficiency of 5-FU in the nanogel preparation was 82.12 ± 1.2 %. The 5-FU nanogel formulation exhibited excellent radiolabelling efficiency (&gt; 93 %) and high stability. Skin/blood localization ratios of 274.93 and 167.89 were obtained for topical radiolabelled drug-loaded 5-FU nanogel formulation and 5-FU commercial formulation, respectively, after 1 h of administration. Gamma scintigraphy and biodistribution studies showed that topically administered 99mTc-5-FU nanogel was distributed mostly in skin, when compared to marketed 5-FU formulation. Pharmacokinetic studies revealed low maximum activity in the blood (Cmax = 34.20 µg/mL), with low intensity (AUC) for topically administered 99mTc-5-FU nanogel formulation.&#x0D; Conclusion: 5-FU nanogel enhances specific delivery of 5-FU at targeted sites and decreases its toxicity in tissues distant from the site of application. The results suggest that nanogel loaded with 5-FU containing synthesized GA-SA conjugate is a novel effective approach for the treatment of skin lesions.

Results from the 208-Week (4-Year) Follow-up of RESPONSE Trial, a Phase 3 Study Comparing Ruxolitinib (Rux) with Best Available Therapy (BAT) for the Treatment of Polycythemia Vera (PV)

Results from the 208-Week (4-Year) Follow-up of RESPONSE Trial, a Phase 3 Study Comparing Ruxolitinib (Rux) with Best Available Therapy (BAT) for the Treatment of Polycythemia Vera (PV)

025 ALA-PDT inhibits skin squamous cell carcinoma (cSCC) via regulating formation of tertiary lymphoid structures

Topical ALA-mediated PDT, ALA-PDT, is a novel therapeutic modality widely used to treat actinic keratosis, Bowen’s Disease, superficial skin SCC, and other cancerous and precancerous skin diseases. Several studies have proved that ALA-PDT can inhibit SCC growth. Subsequent research suggested that ALA-PDT not only directly induced tumor cells apoptosis, but also improve tumor microenvironment through regulation of immune cells. However, the anti-tumor immune function of ALA-PDT is still need to be elucidated. Here, we found that tertiary lymphoid structures (TLSs), which are ectopic lymphoid organs that develop in non-lymphoid tissues at sites of chronic inflammation including tumors, play a pivotal role in anti-tumor immune function of ALA-PDT. We analyzed 77 samples of cSCC patient in our hospital. TLS was observed in 79% of the patient samples, and the density of TLS is negatively correlation with the Brodes classification of cSCC. Intriguingly, immunohistochemistry showed that ALA-PDT could promote the formation of TLS in vivo. We also found that promotion effect of ALA-PDT on TLS is mediated by M1 macrophage, which function as lymphoid tissue inducer cells in TLS formation and recruited by ALA-PDT. Further investigation substantiated that PDT-secreted exosomes were involved in M1 macrophage polarization. Our study elucidated a mechanism that ALA-PDT influence M1 macrophage polarization via PDT-secreted exosomes, which could facilitate the formation of TLS. Thus, our research may contribute to in-depth molecular understanding of the ALA-PDT on anti-tumor immune function.

Professional-Grade TCA-Lactic Acid Chemical Peel: Elucidating Mode of Action to Treat Photoaging and Hyperpigmentation.

Chemical peeling is usually performed by dermatologists, plastic surgeons, and aestheticians for the treatment of photo-aged skin, dyspigmented skin, skin prone to acne eruption, and pre-cancerous skin lesions, etc. In this research paper, we report our investigative findings to understand the mode of action of a commercial professional chemical peel to treat hyperpigmented and photoaged skin. In the in-vitro experiments, we found that the peel inhibits enzymes that are responsible for degradation of collagen and elastin, and the production of melanin pigment. It was surprising to observe that trichloroacetic acid (TCA), which is considered a workhorse of chemical peels for its cauterant action, could synergistically promote the inhibitory action of lactic acid. The rationale behind this synergistic effect could be the conformational change in TCA from linear structure to ring-like structure, which was elucidated through sequential docking using Rosetta software. The in-vitro results on collagen and elastin were corroborated by up-regulation of COL1A, COL3B, fibronectin, and elastin gene expression from 3D human skin equivalents treated with the peel. The findings were further validated through ex-vivo testing on human skin biopsy. The peel significantly inhibits the production of total melanin, and ameliorates photo-damage that was evident through repair of the collagen in the skin exposed to a biological effective dose of UV daily light (6 J/cm2). These research findings have implications for product developers and users (dermatologists, plastic surgeons, and aestheticians) in improving safety and efficacy of chemical peels/peeling.

Real-life evaluation of the treatment of actinic keratoses by textile photodynamic therapy (FLUXMEDICARE® device).

Actinic keratoses (AK) are a common precancerous skin condition in dermatology practice. Photodynamic therapy (PDT) with ALA or MAL is an effective but painful treatment of fields of cancerization particularly when conventional illumination sources and irradiation rates are used. Two prior studies showed that illumination with textile PDT was not inferior to conventional PDT. FLUXMEDICARE® (FLX-PDT) is the first medical device marketed with textile based lighting . We performeda real-life study to evaluate efficacy and tolerance of this device. We carried out a single-center retrospective study. We collected data from patients treated with FLX-PDT with MAL for AKs localized on scalp and temples between November 2018 and November 2019. The primary endpoint was complete clearance rate (CR) at 3 months-follow up. Data of 39 patients were reviewed in the study, with a total of 417 AKs. The CR rate was 72.6 % (95 %CI 67.9-77.0) at 3 months-follow up and 67.5 % (95 %CI 61.2-73.3) at 6 months-follow up. The median pain felt during the session was 0 and there wasn't erythema after the session for 64.1 %. Our real-life study confirms efficacy and safety of textile PDT by FLUXMEDICARE device in the treatment of scalp and temples AKs, with excellent tolerance and minimal pain reported.

The clinical utility of teledermoscopy in the era of telemedicine.

Teledermoscopy is a novel diagnostic tool for the prevention, diagnosis, and treatment of skin disease when direct visualization of lesions is difficult. It is an economically viable option that can complement telehealth visits and that providers can utilize to identify melanocytic lesions and optimize care with diagnostic accuracy comparable to face-to-face (FTF) diagnosis. Teledermoscopy is invaluable in monitoring chronic conditions that require frequent follow-up and treatment optimization. Inclusion of clinical and dermoscopic images has been shown to improve the diagnostic accuracy of teledermatology services, thereby reducing healthcare costs. Teledermoscopy is also non-discriminatory, as diagnostic accuracy is similar in lighter and darker skin types. It has been shown to improve patient access to specialty services and reduce the number of "no-shows" at FTF clinics and length of surgery waiting times. Mobile teledermoscopy is user-friendly, feasible, and economically viable, as inexpensive mobile dermatoscopes have emerged on the market to reduce consumer out-of-pocket costs. Research is limited on teledermoscopy's utility in diagnosing pre-cancerous and cancerous skin lesions in adults, particularly complex pigmented lesions. Further research is recommended to investigate the role of dermoscopic expertise and artificial intelligence on the evaluation of teledermoscopic images.

Lasers and energy-based devices for treating Pre-cancerous and Non-Melanoma Skin Cancers: A review of literature

Skin cancer has been the most common type of malignancies overall with an increasing incidence. The standard of treatment is surgical excision or Mohs Microscopic surgery for high-risk cancer or sensitive areas. Lasers have been used with promising results for treating non-melanoma skin cancers. This paper provides an overall review of the available lasers and energy-based devices utilized for treating NMSK; Squamous Cell Carcinoma In Situ, Invasive Squamous Cell Carcinoma, Basal Cell Carcinoma, Keratoacanthoma, Verrucous carcinoma, and the pre-cancerous Actinic keratosis, and Porokeratosis

Skin Diseases among the Old Age Residents in a Nursing Home: A Neglected Problem.

Background Geriatric health care has become a worldwide concern, but a few statistical studies were carried out about skin diseases in this age group in the nursing home of Iran. Aims In this study, we set out to determine the frequency as well as the age and gender distribution of dermatological diseases in nursing home old age residents. Methods In a cross-sectional study, all patients over 60 years who were living in a charity nursing home complex of Rasht in 2017 participated in this study. Baseline information on sociodemographic variables, past medical history, and medication were gathered by medical staff during a face-to-face interview. Full-body skin examination was done by dermatologists. Biopsy, and pathological and laboratory methods were used to confirm the diagnosis of suspected lesions or disease. Results In this study, 259 people underwent the study. 52.9% were male, and their mean age was 73.5 years (SD = 9.1 years). Hypertension (20.9%); diabetes mellitus (9.7%), and hypothyroidism (2.3%) were the most common underlying diseases. Most of them (85.7%) had age-related skin changes. The benign neoplasm was the most common skin disease among patients (68.3%), followed by infectious diseases (46.3%) and erythemo-squamous (31.6%). None of them had precancerous lesions or skin cancers. There were not any differences between skin disorders and gender or age groups in this study. Conclusion Our study suggests that skin manifestations and diseases are common among nursing home old age residents in this area. Therefore, this should constitute one of the top priorities of aged care physicians and nurses.

Bioactive diterpenoid metabolism and cytotoxic activities of genetically transformed Euphorbia lathyris roots

Plants in the genus Euphorbia produce a wide variety of pharmacologically active diterpenoids with anticancer, multidrug resistance reversal, and antiviral properties. Some are the primary industrial source of ingenol mebutate, which is approved for treatment of the precancerous skin condition actinic keratosis. Similar to other high value phytochemicals, Euphorbia diterpenoids accumulate at low concentrations in planta and chemical synthesis produces similarly low yields. We established genetically transformed root cultures of Euphorbia lathryis as a strategy to gain greater access to diterpenoids from this genus. Transformed roots produced via stem explant infection with Agrobacterium rhizogenes strain 15834 recapitulated the metabolite profiles of field-grown plant roots and aerial tissues. Several putative diterpenoids were present in transformed roots, including ingenol and closely related structures, indicating that root cultures are a promising approach to Euphorbia-specific diterpenoid production. Treatment with methyl jasmonate led to a significant, albeit transient increase in mRNA levels of early diterpenoid biosynthetic enzymes (farnesyl pyrophosphate synthase, geranylgeranyl pyrophosphate synthase, and casbene synthase), suggesting that elicitation could prove useful in future pathway characterization and metabolic engineering efforts. We also show the potential of transformed E. lathyris root cultures for natural product drug discovery applications by measuring their cytotoxic activities using a panel of human carcinoma cell lines derived from prostate, cervix, breast, and lung.

Comparing efficacy and safety of potassium hydroxide 5% solution with 5-fluorouracil cream in patients with actinic keratoses: a randomized controlled trial

Background Actinic keratosis (AK) is a pre-cancerous skin lesion, associated with development of squamous cell carcinoma. Current treatment options are limited. Objectives To compare the efficacy and safety of topical 5-fluorouracil cream (5-FU) and potassium hydroxide 5% (KOH) in the treatment of AK. Methods Eighteen patients with AK applied KOH solution or 5-FU on each side of their scalp/face, randomly. The efficacy and safety of these treatments were compared. Results Thirteen (118 lesions) and ten (83 lesions) patients were successfully followed for one and three months, respectively. After one month, KOH showed a better clinical response (81% vs. 58%; p-value = 0.007) and dermoscopic response (KOH, 65% vs. 5-FU, 46%; p-value = 0.04); while no differences were noted after three months (clinical response, 83% vs.70%, p-value = 0.1; dermoscopic response, 76% vs. 59%, p-value = 0.1). No significant differences in the recurrence rate of the lesion between the two groups were noted at the end of the third month (p-value = 0.5). Regarding the safety of the treatments, the risk of developing erythema, scaling, sand swelling was higher in 5-FU group (p-value < 0.0001, for all), while more patients in KOH group had erosion and ulcer (p-value < 0.001 for both). KOH was up to 96% less expensive than 5-FU. Limitations Low number of patients and short-term follow-up limited the analysis. Conclusion KOH solution offers a faster and less expensive resolution of AK lesions than does 5-FU. Clinical Trial Code (IRCT.ir) IRCT20180909040978N1

Microwave therapy: A new treatment for precancerous skin lesions (actinic keratoses)

British Journal of DermatologyVolume 183, Issue 2 p. e43-e43 Plain Language Summary Free Access Microwave therapy: A new treatment for precancerous skin lesions (actinic keratoses) First published: 02 August 2020 https://doi.org/10.1111/bjd.19277 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract This study was performed in the UK and aimed to find out whether a small dose of microwave energy, delivered through a hand-held probe, could be an effective and tolerable new treatment for actinic keratoses (AK). AK are very common in fair-skinned older people and are the result of sun damage in our skin. There is emerging evidence that treating AK can reduce future development of skin cancer. We treated AK on one half of a person's bald scalp or on the back of one hand with microwave energy (the side treated was chosen at random) and observed the difference between treated and untreated AKs over a period of 4 months. Current treatments for AK are not ideal. Freezing AK with liquid nitrogen can be painful and may leave a scar, and the cream treatments available require dedicated application over weeks and cause the skin to become inflamed and sore. In comparison, treatment using the microwave device required two sessions 4 weeks apart, causing a short sharp pain lasting about 1 second. Most participants thought it was either ‘as good’ or ‘better’ than previous treatments they had tried. Four months after their initial treatment, 90% of AK had either partially resolved (disappeared where the probe was placed, with some persisting AK outside of the treated area) or completely resolved (the AK had gone entirely). These results are promising, but a larger study is needed to compare this new treatment to a more established one, like the creams or freezing spray mentioned, to ensure it is as effective. Linked Article: Jackson et al. Br J Dermatol 2020; 183:222–230. Volume183, Issue2August 2020Pages e43-e43 RelatedInformation

Subungual Squamous Cell Carcinoma in a Patient with Psoriasis.

Subungual squamous cell carcinoma (SCC) is often misdiagnosed as a benign condition so most cases are invasive by the time of diagnosis; nail elevation and biopsy are recommended in all suspicious cases.Although psoriasis is not an independent risk factor for subungual SCC, the cyclosporine and PUVA used to treat psoriasis are risk factors for cutaneous SCC.The aetiology for subungual SCC is still unclear, but it should be suspected in patients with psoriasis and a suspicious presentation.

A facile fabrication of dissolving microneedles containing 5-aminolevulinic acid.

Photodynamic therapy induced by protoporphyrin IX (PpIX) is widely used to treat precancerous skin lesions. The penetration depth of the prodrug 5-aminolevulinic acid (5-ALA) using topical application is currently limited, which hampers the production of PpIX in deep seated lesions. To enhance 5-ALA delivery in deep skin layers, a soluble microneedles patch (MN-patch) containing 5-ALA has been successfully developed by using a fast solvent casting molding method which could be easily up-scaled. The shape, number and height of the needles have been designed according to the medical application and the mechanical strain necessary for skin insertion. Hyaluronic acid (HA) has been chosen as the needle materials due to its biocompatibility, fast solubility and biodegradation and was mixed with 5-ALA prior to casting. HA-based MN-patch containing 5-ALA have exhibited mechanical properties enabling a good insertion into the skin without significant damages to MN. Interactions between HA and 5-ALA were evaluated by Fourier transform infrared spectroscopy (FTIR) and carbon nuclear magnetic resonance (13C NMR), stability of 5-ALA in the MN-patch was monitored by proton nuclear magnetic resonance (1H NMR) and exhibited a good stability over 5 months after manufacturing. Dissolution rate of the whole patch was completed in 1 hour in ex vivo rat skin without cytotoxicity. Overall, the MN-patch can be a promising technique to enhance 5-ALA penetration and produce PpIX in deeper skin lesions.

Efficacy of topical photodynamic therapy in the treatment of Erythroplasia of Queyrat.

Erythroplasia of Queyrat (EQ) is an intraepidermal carcinoma in situ presenting clinically as a sharply demarcated, slightly raised erythematosus plaque on the glans penis or the inner side of the foreskin. Various treatment modalities for EQ have been proposed, including electrocautery and curettage, topical 5-floururacil cream, imiquimod cream, isotretinoin, cryotherapy, laser therapy, radiotherapy, ingenol mebutate gel and Photodynamic Therapy (PDT). Most of these treatments are limited by low clearance rates and frequent relapses. Surgical treatment including local excision, Mohs micrographic surgery and partial or total penectomy, ensures adequate healing rates. However, discomfort consequent to surgical treatment might be unacceptable. Topical PDT using the methyl ester of 5- aminolaevulinic acid (MAL) is an established non-surgical treatment of cutaneous precancerous lesions and skin cancers. We present the case of a 60-year-old uncircumcised man affected by EQ of the penis successfully treated with MAL-PDT, performed five times, two weeks apart, with no recurrences after 6 years.

617 Skin squamous cell carcinoma (SCC)-derived exosomes after ALA-PDT treatment deliver microRNA-3473 to induce M1 macrophage polarization via NF-κB pathway

Topical ALA-mediated PDT, ALA-PDT, is a novel therapeutic modality widely used to treat actinic keratosis, Bowen’s Disease, superficial skin SCC, and other cancerous and precancerous skin diseases. Several studies have proved that ALA-PDT can inhibit SCC growth and reduce tumor volume. Subsequent research suggested that ALA-PDT not only directly induced tumor cells apoptosis, but also improve tumor microenvironment through regulation of immune cells. However, the anti-tumor immune function of ALA-PDT is still need to be elucidated.