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 ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC.
Methods: UV-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 NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.
Results: PLGA NPs could enhance PpIX 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.
Objectives: To examine therapeutic effects of 5-aminolevulinate (ALA)-mediated photodynamic
therapy (PDT) on UVB-induced cutaneous squamous cell carcinomas (SCCs) in a mouse model.
Materials and methods: Cutaneous SCCs were established by UVB (280-320 nm) irradiation of
hairless mice. In situ fluorescence measurement was used to monitor PpIX formation after the
topical application of various concentrations of ALA cream to determine the optimal ALA dose.
Therapeutic responses of SCCs to multiple sessions of ALA PDT were examined histologically
and quantitatively. TUNEL staining was used to examine apoptosis caused by PDT. Results: After
repeated exposure for 18 to 22 weeks (4-5 days/week), multiple nodular and verrucous hyperplasia
lesions of various sizes developed at the exposed area. After four sessions of ALA PDT (8% ALA,
3 h incubation, 30 J/cm2 at 20 mW/cm2) a total of 84% of complete response was achieved for
small SCCs (1-4 mm, thickness <2.5 mm). TUNEL staining showed that PDT-induced apoptotic
cells were distributed evenly from the basal to stratum corneum layers. Conclusions: Topical ALA
PDT can trigger apoptosis in SCCs, inhibit SCC growth, and reduce the size and number of tumors
in the hairless mouse model. The true clinical value of ALA PDT for the treatment of cutaneous
SCC deserves further investigation.
We report on some of the optical properties of hematoporphyrin monomethyl ether
(HMME), a relatively new photosensitizer that has been in clinical trials in China
since the early 1990s. We characterized the photosensitizer on the basis of one
photon absorption and emission. In addition, the effects of photobleaching were
probed to characterize its decay kinetics.
Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-
medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne
vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were
treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied
to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose
levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and
after treatment up to 3 months. Results: All patents showed response to ALA PDT.
Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients
(37.5%). One case showed recurrence after complete clearance at 2 months and another
two showed recurrence after complete clearance at 3 months. However, the number of new
lesions were significantly reduced. Adverse effects were minimal. Conclusions: The
results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and
useful therapeutic option for the treatment of moderate to severe acne. Further studies to
evaluate the treatment with a larger number of patients and for a longer period of follow-up
are needed.
Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.
Objectives: To investigate the pharmacokinetics of ALA induced protoporphyrin IX (PpIX) in lesions of urethral condylomata acuminata. Methods: Sixty patients (20 - 60 years old, 48 male
and 12 female) with urethral condylomata acuminata were divided randomly into 5 groups to receive different concentrations of ALA solution (0.5, 1, 3, 5 or 10%). The ALA solution was
applied topically to the lesion for a different length of time (1, 3, 5 or 7 h). Biopsy was performed at the end of incubation and specimens were subjected to histological and PpIX fluorescence analyses. Results: ALA-induced PpIX fluorescence was dominantly distributed in the epidermis. The maximal fluorescence intensity was detected at the 5 h of incubation. Higher ALA concentration (e.g. 5 and 10%) produced stronger intensity. In contrast, only the minimal
amount of PpIX fluorescence was detected in the dermis. Conclusions: The results suggest that the topical application of 5 - 10% ALA solution for 3-5 h are the optimal conditions for ALA/PpIX-mediated photodynamic therapy for the treatment of urethral condylomata
acuminata.
To investigate the feasibility and efficacy of combination of imiquimod immunotherapy and 5-
aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) for the treatment of genital bowenoid papulosis
(BP). A total of twenty seven BP patients were randomized into two groups: (I) fifteen
patients (12 male and 3 female, age 22-56 years old) were treated with topical application of 5% imiquimod cream
(three times a week) and ALA-PDT (100 J/cm2 at 100 mW/cm2, once a week) for 1-4 times in one week interval.
(II) Twelve patients (6 male and 6 female, age 29-58 years old) were treated with CO2 laser vaporization as a control.
Patients were followed up for 3 to 12 months. Results: In combined therapy group, 60% (9/15) patients showed
complete remission and only one recurred (11.1%) during follow up. Local side effects included mild erythema,
edema, erosion and burning and/or stinging sensation. No systemic side effect was found. In CO2 laser vaporization
group, 83.3% (10/12) patients showed complete remission. However, recurrence occurred in 6 patients (60.0%).
Local side effects included mild to moderate edema, erosion, ulceration, delayed healing, prolonged pain and
scarring. The difference of recurrence rate between two groups was statistically significant (P < 0.05).
Topical application of imiquimod cream and ALA-PDT is safe, effective and associated with low recurrence and less
side effect. Its true clinical value needs to be further investigated by a long-term follow-up of large scale trial.
Background: Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. Objective: To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA-PDT. Methods: One hundred and sixty-four urethral condylomata patients were given topical ALA followed by intraurethral PDT through a cylindrical fiber. Among the cases, 16 penile and vulval condylomatous lesions in 11 patients were treated with topical ALA-PDT at same time. After the treatment, biopsy specimens were collected from the 16 penile and vulval lesions. The histological changes were then evaluated by light microscope and electron microscope. Results: The complete response rate for urethral condylomata by topical ALA-PDT was 95.12% and the recurrence rate was 5.13% after 6 to 24 months follow-up. Keratinocytes in middle and upper layers of the epidermis with marked vacuolation and some necrocytosis were detected one and three hours after PDT. Necrosis in all layers of the epidermis was noted five hours after PDT by microscopy. In electron microscopy of kerationcytes, distinct ultrastructural abnormalities of mitochondrion, endoplasmic reticulum and membrane damage were observed. Apoptotic bodies were detected three hours after PDT and a large number of the keratinocytes exhibited necrosis five hours after PDT by electron microscope. Conclusions: Results suggests that topical ALA-PDT is a simple, effective, relatively safe, less recurrent and comparatively well tolerated treatment for urethral condylomata acuminata. The mechanisms might be that ALA-PDT could trigger apoptotic process and necrosis in the HPV infected keratinocytes.
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