Linglin Zhang

Topical ALA PDT for the treatment of severe acne vulgaris

OBJECTIVES To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-medicated photodynamic therapy (PDT) for the treatment of severe acne vulgaris. METHODS A total of 78 Chinese patients with Grade 4 severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (10%) was applied topically to acne lesions for 3 h. The lesions were irradiated by a LED light of 633 nm at dose levels of 50-70 J/cm(2) at 66 mW/cm(2). Clinical assessment was conducted before and after treatment up to 6 months. RESULTS 22% of patients showed excellent improvement after one-course treatment and another 34% showed excellent improvement after two-course. The rest (44%) required three-course treatment to further reduce the number and size of residual lesions. Adverse effects were minimal. The symptoms and signs in recurrent cases (14%) were much milder and responded well to conventional topical medication. CONCLUSIONS ALA PDT is a simple, safe and effective therapeutic option for the treatment of severe acne. Further studies to fully understand its mechanisms and optimize its effectiveness are needed.

Treatment of HPV Infection‐Associated Cervical Condylomata Acuminata with 5‐Aminolevulinic Acid‐Mediated Photodynamic Therapy

The aim of this study was to investigate the efficacy of 5‐aminolaevulinic acid (ALA)‐mediated photodynamic therapy (PDT) in treatment of human papillomavirus (HPV)‐associated cervical condylomata. A total of 56 patients with cervical and external condylomata lesions were recruited for this open‐label study. HPV genotyping of exfoliated cells collected from the cervix and external lesions was performed. Cervical lesions were treated with PDT by applying ALA gel (10%) to the surface of the cervix for 4 h followed by irradiating with a 635 nm laser at 100 J cm−2. PDT was repeated at 2‐week intervals if lesion and HPV infection remained. Patients were followed up for 6–24 months. Genotyping analysis revealed four HPV subtypes (HPV6, 11, 16 and 18). The overall complete remission rate of 1–4 sessions of treatments was 98.2% and the corresponding HPV clearance rate was 83.9%. Ten cases showed complete removal of cervical lesions and HPV infection after a single treatment. Recurrence rate was 3.6%. Adverse effects were minimal and no structural complications were reported. In conclusion, topical ALA PDT is safe and effective for eradicating cervical HPV infection and eliminating condylomata lesion. Its definitive role in treating cervical condylomata deserves further investigation.

Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.

Aminolevulinic acid (ALA)-assisted photodynamic diagnosis of subclinical and latent HPV infection of external genital region

The relatively high recurrence rate of genital warts can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. Therefore, the identification and treatment of the subclinical and latent infection is a key to reduce the recurrence. The goal of this study is to investigate the usefulness of 5-aminolevulinic acid (ALA)-assisted in situ fluorescence diagnosis of subclinical lesion and latent HPV infection. A total of 30 patients with histologically confirmed genital warts (condylomata acuminata) were subjected to topical application of ALA, acetic acid test, histopathologic examination and HPV DNA subtyping. Topical application of ALA was performed by applying 20% ALA cream to the lesion plus 2-cm margin for 2h followed by fluorescence examination. Correlations between histopathologic examination, aceto-whitening test, HPV DNA subtyping and fluorescence were examined. All warty lesions and subclinical lesions (n=25) showed red fluorescence and harbored HPV DNA (HPV6 or 11). Latent HPV infections at 0.5-2 cm away from the warty lesion also showed red fluorescence. Nonspecific fluorescence was associated with mucosa, inflammatory infiltration and erosive lesion. ALA-assisted photodynamic diagnosis could be employed for the detection of the lesion and subclinical lesion of genital warts. It is also useful in detecting latent HPV infection.

Evaluation of 5-aminolevulinic acid-mediated photorejuvenation of neck skin

OBJECTIVE To evaluate the outcomes of the combination of red light or intense pulsed laser (IPL) with 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in the treatment of photodamaged neck skin. METHODS The anterior of the neck was divided into four 2 cm × 2 cm sections and randomly assigned to red-light, red-light-PDT, IPL or IPL-PDT group. ALA cream of 5% was applied to PDT regions for 2h prior to light irradiation. Treatment was repeated once. The stratum corneum (SC) hydration, transepidermal water loss (TEWL), L(*), a(*), b(*) values, melanin index (MI), erythema index (EI), skin elasticity and skin thickness were examined by a blinded investigator. The function and volume of thyroid were also measured. RESULTS After red-light-PDT, IPL-PDT and IPL treatment, the appearance of photoaging lesion was improved. The SC hydration, L(*) value, elasticity and thickness increased, whereas the TEWL and MI value decreased. These changes in red-light-PDT and IPL-PDT group were more obvious than IPL group. The a(*) and EI value increased in red-light-PDT group. No significant change was noticed in red-light group. Partial irradiation of the thyroid did not affect the function and volume of the thyroid. CONCLUSION IPL-PDT and red-light-PDT showed better rejuvenation effect than IPL or red light alone on the neck skin.

Comparison of 5-aminolevulinic acid photodynamic therapy and red light for treatment of photoaging.

OBJECTIVE The aim of this pilot study was to compare the efficacy of ALA-PDT and red light alone in the treatment of photoaging. METHODS A total of 14 adults with photoaging skin were recruited. ALA-PDT or red light alone was applied to the forearm extensor. Before and after treatment, the treated sites were examined by dermoscopy, the changes in straum corneum (SC) hydration, transepidermal water loss (TEWL), and the L*a*b* values were measured, and microscopic examination of collagens and elastins was performed. RESULTS After ALA-PDT or red light illumination, the appearance of photoaging lesions improved, SC hydration increased and TEWL decreased. These changes in the ALA-PDT group were more obvious than those in the red light group. No significant change was noticed in the L*a*b* values in both groups. The signs of typical solar elastosis damage were improved in both groups. CONCLUSIONS ALA-PDT showed better skin rejuvenation effect than red light alone.

Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model.

Background Squamous cell carcinoma (SCC) is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted 5-aminolevulinic acid (ALA) delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Materials and methods Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

A prospective pilot study to evaluate combined topical photodynamic therapy and surgery for extramammary paget's disease.

Extramammary Pagets disease (EMPD) is a rare intra‐epithelial neoplasm. Surgical excision is the treatment of choice. The usefulness of topical photodynamic therapy (PDT) in the treatment of EMPD has been reported. The objective of this prospective pilot study was to investigate the feasibility of combined PDT and surgery in the treatment of EMPD.

Treatment of cutaneous lichen planus with ALA-mediated topical photodynamic therapy

Purpose: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of cutaneous lichen planus (LP). Methods: A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed. ALA cream (10%) was applied topically to LP lesions for 3 h. The lesions were irradiated with a 635 nm diode laser at the dose level of 100 J/cm2. The treatment was repeated at two-week intervals. Clinical assessment was conducted before each treatment. Follow-up was performed once a month for up to six months. Results: Lesions showed significant improvement after one to four courses of treatments. Complete response was achieved in 13 lesions (five patients) and partial remission in four lesions (two patients). The complete response rate was 71%. There was no significant side effects except the feeling of pain that most patients could tolerate. Follow-up of five patients who achieved complete response showed no signs of recurrence. Conclusion: Topical ALA PDT is effective in the treatment of cutaneous LP.

Clinical and Molecular Characterization of NF1 Patients: Single-Center Experience of 32 Patients From China.

AbstractNeurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the genes large size, the lack of mutation hotspots, and the presence of pseudogenes.Our goal was to establish a sensitive, feasible, and comparatively economical protocol to detect NF1 mutations using blood samples.We developed a method to screen patients for mutations. Thirty-two NF1 patients from 32 unrelated families and 120 unrelated population-match controls were investigated in this study. Specific primers were designed for NF1 to avoid pseudogenes. NF1 mutations were detected by sequencing at the deoxyribonucleic acid (DNA) and complementary DNA (cDNA) levels, and multiplex ligation-dependent probe amplification (MLPA) and familial segregation analyses were used.Forty-four specific primers designed according to the NF1 structure were successfully used for polymerase chain reaction (PCR) and DNA sequencing, which was more feasible and useful than cDNA sequencing. Thirty distinct NF1 mutations were identified in 32 patients. Thirteen mutations were novel and most were frameshift mutations (33.3%). Mutations were detected at a rate of 93.8%.Our study suggests that this sensitive, feasible, and comparatively economical protocol is effective for the detection of NF1 mutations.