ALA Photodynamic Therapy Research Articles

Iron Metabolism in Aminolevulinic Acid-Photodynamic Therapy with Iron Chelators from the Thiosemicarbazone Group.

Iron plays a crucial role in various metabolic processes. However, the impact of 5-aminolevulinic acid (ALA) in combination with iron chelators on iron metabolism and the efficacy of ALA-photodynamic therapy (PDT) remain inadequately understood. This study aimed to examine the effect of thiosemicarbazone derivatives during ALA treatment on specific genes related to iron metabolism, with a particular emphasis on mitochondrial iron metabolism genes. In our study, we observed differences depending on the cell line studied. For the HCT116 and MCF-7 cell lines, in most cases, the decrease in the expression of selected targets correlated with the increase in protoporphyrin IX (PPIX) concentration and the observed photodynamic effect, aligning with existing literature data. The Hs683 cell line showed a different gene expression pattern, previously not described in the literature. In this study, we collected an extensive analysis of the gene variation occurring after the application of novel thiosemicarbazone derivatives and presented versatile and effective compounds with great potential for use in ALA-PDT.

Successful combined treatment with surgery and ALA-PDT for cutaneous infection by candida tropicalis: A case report and literature review

Candidiasis is a common fungal infection, with Candida tropicalis infections being relatively rare. These infections develop into skin fungal infections under conditions such as broad-spectrum antibiotic use, diabetes, and immunosuppression. Traditionally, antifungal drugs have been the primary treatment; however, issues like hepatotoxicity and the need for long-term use persist. Consequently, new treatment approaches are essential. Most previous reports have focused on Candida albicans, with fewer addressing Candida tropicalis. This study reports a case where a patient with a skin Candida tropicalis infection was treated with a combination of surgery and ALA photodynamic therapy(635 nm, 120 J/cm2, 177 mW/cm2). After just one session of this combined treatment, the patient achieved significant clinical remission. Therefore, the combination of surgery and ALA-PDT may offer a safe and effective treatment option.

Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy.

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6months of follow-up. The elimination rate increased to 69.6% (39/56) within 12months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6months (p < 0.001) and histologic regression within 12months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

Comparative study of photodynamic therapy (PDT) of cervical low-grade squamous intraepithelial lesion (LSIL)

BackgroundPrevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. AimsThe aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). MethodsIn PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. ResultThe observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. ConclusionsThis study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

Photodynamic Therapy for the Treatment of Basal Cell Carcinoma: A Comprehensive Review of Randomized Controlled Trials.

Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC. This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed. Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies. Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes. PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.

In vitro modeling of recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-aminolevulinic acid photodynamic therapy efficacy

BackgroundDermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. MethodsThis study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. Results5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. ConclusionsThe findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Theranostic Uses of the Heme Pathway in Neuro-Oncology: Protoporphyrin IX (PpIX) and Its Journey from Photodynamic Therapy (PDT) through Photodynamic Diagnosis (PDD) to Sonodynamic Therapy (SDT).

ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers. This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described.

Recurrent Squamous Cell Carcinoma of the Upper Eyelid Treated With Combination Therapy of ALA Photodynamic Therapy and Surgery With Secondary Healing

Background. Cutaneous squamous cell carcinoma (cSCC) frequently occurs in photoexposed areas. Surgery remains the mainstay of treatment in attempts to reduce recurrence, but it must be combined with other therapy because of the limited excision possible in the region of the eyelid, lip, and nose. Photodynamic therapy (PDT) is a relatively new treatment modality that involves the administration of a photosensitizing drug and its subsequent activation by specific wavelengths of light to produce reactive oxygen species that specifically destroy target cells. Case Report. An 87-year-old female presented 4 weeks after initial resection with recurrent medium-differentiated cSCC measuring 5.2 cm × 3 cm × 2 cm in the left upper eyelid. Subsequent treatment involved palliative resection with an additional 1 cm at 3 margins of the tumor (excluding the bottom edge of the double eyelid line) and 3 applications of PDT using 5-aminolevulinic acid as the photosynthesizing agent in the open wound over a 2-week period. The wound healed well within 6 weeks. During the following 4 years, the patient showed satisfactory progress in both aesthetics and function, with no sign of recurrence or metastasis. Conclusion. Refractory cSCC was successfully managed using a combination of PDT and secondary healing, and functions of the head and face were well protected. These results suggest that such management warrants consideration in clinical settings.

Analysis of drug factors in 5-aminolevulinic acid photodynamic therapy for oral potentially malignant disorder.

This study aimed to analyze the influence of drug factors on the efficacy of 5-aminolevulinic acid (ALA) photodynamic therapy for oral potentially malignant disorder to improve clinical efficacy and promote clinical rational drug use. Literature on the treatment of oral potentially malignant disorder by using ALA photodynamic therapy was collected and analyzed from PubMed, ISI Web of Knowledge database, CNKI, VIP, and Wanfang database. A total of 690 cases were collected, with an average complete response rate of 65.94%. The groups treated with 16.8% methyl aminolevulinate cream, local topical, once a week, and pre-activation time of 2-4 hours were better than the other subgroups, with average complete response rates of 100%, 66.91%, 78.28%, and 77.54%, respectively. Drug factors have direct influence on the curative effect. The development of novel oral ALA formulations from the perspective of drug improvement is an important strategy to improve efficacy.

Prospective cohort study of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with human papillomavirus infection

BackgroundSome patients with cervical low-grade squamous intraepithelial lesions (LSIL) undergo invasive laser ablation or loop electrosurgical excision procedures. Photodynamic therapy (PDT) is a photosensitizer 5-aminolevulinic acid (5-ALA)-based minimally invasive technique that causes minimal normal tissue and cell damage. We investigated 5-ALA-mediated PDT efficacy for cervical LSIL complicated by human papillomavirus (HPV). MethodsThis prospective cohort study was conducted on patients with cervical LSIL, who were divided into treatment (20 % 5-ALA PDT thrice every 7–14 days; n = 216) and control (observation; n = 220) groups. The treatment group underwent cervical cytology and HPV genotyping 3 months after treatment; both groups underwent cervical cytology, HPV genotyping, colposcopy biopsy, and histopathological examination 6 and 12 months post-treatment. ResultsThe 3-, 6-, and 12-month follow-ups revealed gradually improved cervical cytology findings: no intraepithelial lesions or malignant tumor (NILM) rates (approximately 80 %). The HPV clearance rate (baseline subtype) was approximately 68 %: approximately 60 % for HPV16/18 and 71 % for non-HPV16/18 baseline subtypes. By months 6 and 12 after PDT, the LSIL regression rate of cervical histopathology increased (75.46 %–82.08 %). The 6- and 12-month follow-ups revealed significantly increased cervical LSIL regression rates in the treatment group. Compared with the control group, the number of HPV subtypes in the treatment group decreased significantly by 6 and 12 months. Conclusions5-ALA PDT effectively eliminated cervical LSIL and HPV, with sustained effects for up to 12 months post-treatment. Therefore, 5-ALA PDT is an effective and safe treatment for cervical LSIL with HPV that promotes cervical LSIL regression to normal cervical tissue.

Rational of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of endocervical canal low-grade squamous intraepithelial lesion with high-risk human papillomavirus infection.

The detection and continuous monitoring of low-grade squamous intraepithelial lesions (LSIL) within the endocervical canal pose considerable challenges, and the effectiveness of ablation treatment is also constrained. In this context, the potential efficacy of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) in targeting these concealed lesions merits exploration. The present study undertakes a comprehensive analysis of the clinical effectiveness and safety aspects associated with the utilization of 5-ALA PDT. A retrospective analysis was conducted on a cohort of 13 patients who were diagnosed with LSIL within the endocervical canal, concomitant with high-risk human papillomavirus (hrHPV) infection. These patients were subjected to treatment with 5-ALA PDT and subsequently monitored over a period of 3-6 months following the intervention. The study cohort comprised 13 patients, among whom 4 presented with isolated lesions within the endocervical canal, 5 exhibited LSIL involving both the endocervical canal and the cervix vaginal portion, 3 displayed LSIL within the endocervical canal in conjunction with vaginal involvement, and 1 patient demonstrated lesions across all three of these anatomical sites. All identified lesions underwent therapeutic intervention via 5-ALA PDT. Before treatment initiation, 9 patients returned positive results in the liquid-based cytologic test (LBC), 4 displayed concurrent multiple hrHPV infections, and 5 manifested infections specifically with HPV 16/18. Subsequent to the application of 5-ALA PDT, regression was observed in the LBC results of all patients, with only 3 individuals retaining a singular type of hrHPV infection. Adverse reactions following treatment encompassed mild aberrant vaginal secretions and mild to moderately pronounced distending abdominal discomfort, all of which were remitted within a span of 7 days. Within the context of LSIL within the endocervical canal in association with hrHPV infection, the findings affirm the efficacy and safety of 5-ALA PDT as a viable therapeutic modality.

The effect of aminolevulinic acid hydrochloride topical powder photodynamic therapy versus nocardia rubra cell wall skeleton and observers group in the treatment of cervical low-grade squamous intraepithelial lesions with human papillomavirus infection: A non-randomized study, controlled pilot study.

There are insufficient studies comparing the efficacy of aminolevulinic acid hydrochloride topical powder (ALA) photodynamic therapy (PDT) against Nocardia rubra cell wall skeleton (Nr-CWS) therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with human papillomavirus (HPV), especially for long-term efficacy. Patients with cervical LSIL and HPV infection were divided into 3 treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4 to 6 months and 12 months after the treatment. Among142 patients, patients received 51 ALA PDT and 41 patients received Nr-CWS. Another 50 patients who refused treatment were included in the Observers group. Four to six months or 12 months after treatment, there was significant difference between 3 groups in the clearance rate of HR-HPV infection and the complete remission (CR) rates of cervical LSIL; the CR rates of cervical LSIL in the ALA PDT group was significantly higher than the Nr-CWS group; but there was no significant difference between 2 groups in the clearance rate of HPV infection. The CR rates of cervical LSIL and the clearance rate of HPV infection in the ALA PDT group was significantly higher than the Observers group; the CR rates of cervical LSIL and the clearance rate of HPV infection in the Nr-CWS group was significantly higher than the Observers group; there was no significant difference in the recurrence rates in ALA PDT and Nr-CWS group after 12 months. Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. The effect of ALA PDT is similar to Nr-CWS in the clearance rate of HR-HPV infection. Compared to the Nr-CWS group, the CR rates of cervical LSIL were considerably greater in the ALA PDT group. The effect of ALA PDT in the clearance rate of HPV infection and CR rates of cervical LSIL was significantly higher than the follow-up group; Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. For cervical LSIL with HPV infection, ALA PDT is a very successful therapeutic method that is noninvasive.

An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma.

Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.

Clinical observation of laser combined with 5-aminolevulinic acid photodynamic therapy for female vulva condyloma acuminatum.

Condylomata acuminata, or genital warts (GW), are exceedingly prevalent, with human papilloma virus infection accounting for 90% of cases. It can be treated in a variety of methods, but the high recurrence rate and cervical scars make it difficult to choose the best treatment option. Hence, the study aims to find the effect of laser combined with 5-aminolevulinic acid (ALA) photodynamic therapy for condyloma acuminata in the vulva, vagina, and cervix. A total of 106 female patients with GW of the vulva, vagina, and cervical condyloma acuminata were treated in the Dermatology Department of Subei People's Hospital in Yangzhou from May 2020 to July 2021. All these patients were treated with laser combined with 5-ALA photodynamic therapy to observe the therapeutic effect. About 84.9% of patients responded to the first session of ALA-photodynamic treatment. Five patients relapsed in the 2nd week, two patients relapsed in the 4th week, one relapsed in the 8th week, one relapsed in the 12th week, and the relapsed patients were given 1-3 times of photodynamic therapy again, and no recurrence was seen in the 24th week. After four courses of treatment in 106 patients, the wart clearance rate was 100%. Laser combined with 5-ALA photodynamic therapy for female vulva, vagina, and cervix condyloma acuminata has a reliable curative effect, low recurrence rate, few adverse reactions, and less pain. It is worth promoting in female vulva, vagina, and cervical condyloma acuminata.

5-ALA photodynamic ablation of fibroblastic soft-tissue tumors

Background: Fibroblastic soft-tissue tumors share enzymatic anomalies that result in excessive intracellular conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin IX, a photosensitizer which induces cellular apoptosis upon exposure to visible red light at a wavelength of 635 nm. We hypothesized that red light illumination of the surgical bed remaining after resection of fibroblastic tumors will result in destruction of microscopic tumor residua and may decrease the likelihood of local tumor recurrence. Methods: Twenty-four patients with desmoid tumors, solitary fibrous tumors (SFT), and dermatofibrosarcoma protuberans (DFSP) received oral 5-ALA prior to resection of their tumors. Following tumor resection, the exposed surgical bed was illuminated with red light at a wave length of 635 nm at a dose of 150 J/cm2 for 33 min. Results: Treatment with 5-ALA was associated with minor side effects that included nausea and transient elevation of transaminases. Local tumor recurrence was detected in 1 of the 10 patients with desmoid tumors who had not undergone any previous surgery, none in the 6 patients who had SFT and 1 of the 5 patients who had DFSP. Conclusions: 5-ALA photodynamic therapy of fibroblastic soft-tissue tumors may result in decreased likelihood of local tumor recurrence. It is associated with minimal side effects and should be considered as adjuvant to tumor resection in these cases.

Plum-blossom needle tapping enhances the efficacy of ALA photodynamic therapy for facial actinic keratosis in Chinese population: a randomized, multicenter, prospective, and observer-blind study

BackgroundPhotodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a reliable treatment for actinic keratosis (AK), but its effect needs to be enhanced in thick lesions. Plum-blossom needle is a traditional Chinese cost-effective instrument for enhancing the transdermal delivery of ALA. However, whether it could improve the efficacy of AK treatment has not yet been investigated. ObjectiveTo compare the efficacy and safety of plum-blossom needle–assisted PDT in facial AK in the Chinese population. MethodsIn this multicenter, prospective study, a total of 142 patients with AKs (grades I–III) were randomized into the plum-blossom needle–assisted PDT group (P-PDT) and control PDT group (C-PDT). In the P-PDT group, each AK lesion was tapped vertically by a plum-blossom needle before the application of 10% ALA cream. In the C-PDT group, each lesion was only wiped with regular saline before ALA cream incubation. Then, 3 hours later, all the lesions were irradiated with light-emitting diode (LED) at a wavelength of 630 nm. PDT was performed once every 2 weeks until all lesion patients achieved complete remission or completed six sessions. The efficacy (lesion response) and safety (pain scale and adverse events) in both groups were evaluated before each treatment and at every follow-up visit at 3-month intervals until 12 months. ResultsIn the P-PDT and C-PDT groups, the clearance rates for all AK lesions after the first treatment were 57.9% and 48.0%, respectively (P < 0.05). For grade I AK lesions, the clearance rates were 56.5% and 50.4%, respectively (P = 0.34). For grade II AK lesions, the clearance rates were 58.0% and 48.9%, respectively (P = 0.1). For grade III AK lesions, the clearance rates were 59.0% and 44.2%, respectively (P < 0.05). Moreover, grade III AK lesions in the P-PDT group required fewer treatment sessions (P < 0.05). There was no significant difference in the pain score between the two groups (P = 0.752). ConclusionPlum-blossom needle tapping may enhance the efficacy of ALA-PDT by facilitating ALA delivery in the treatment of AK.

Clinicopathological features, therapeutic options, and significance of CD103 expression in 15 patients with follicular mucinosis.

Follicular mucinosis (FM) is generally divided into a primary benign idiopathic form and a secondary form associated with mycosis fungoides. To analyze the clinical and pathological features of FM and explore the pathological significance of CD103 expression. In this case series, we retrospective analysis the clinical, pathological, treatment and follow-up treatment of 15 cases of FM. The expression of CD103 in all cases was detected by immunohistochemistry. A total of 15 patients were enrolled, 7 were primary follicular mucinosis (P-FM) and 8 were mycosis fungoides-associated follicular mucinosis (MF-FM). Lesions of both P-FM and MF-FM are difficult to distinguish, present with red or dark red plaques and follicular papules. Pathologically, MF-FM showed more significant infiltrates of folliculotropic lymphoid cells, and the amount and proportion of CD103+ cells were significantly higher than that in P-FM. Follow-up data were available for 13 patients. Three cases were resolved after surgical resection, two patients were marked improved after oral administration of hydroxychloroquine and three times ALA photodynamic therapy respectively. The rest patients showed only modest efficacy. FM should be differentiated based on pathological characteristics and treatment response, CD103 is helpful in differential diagnosis of FM.

5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas.

Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g., doxorubicin (DOX)), improving, thus, the anti-tumorigenic effects. In this study, we investigated the effects of DOX and 5-ALA PDT alone or in combination on three different human ES cell lines. Cell viability, reactive oxygen species (ROS) production, and cellular stiffness were measured 24 h after PDT (blue light-wavelength 436 nm with 5-ALA) with or without DOX. ES cell lines have a different sensitivity to the same doses and exposure of 5-ALA PDT. DOX in combination with 5-ALA PDT was found to be effective in impairing the viability of all ES cells while also increasing cytotoxic activity by high ROS production. The stiffness of the ES cells increased significantly (p &lt; 0.05) post treatment. Overall, our results showed that across multiple ES cell lines, 5-ALA PDT can successfully and safely be combined with DOX to potentiate the therapeutic effect. The 5-ALA PDT has the potential to be a highly effective treatment when used alone or in conjunction with other treatments. More research is needed to assess the effectiveness of 5-ALA PDT in in vivo settings.

KDM1A inhibition increases UVA toxicity and enhances photodynamic therapy efficacy.

Lysine-specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. Despite the role of KDM1A in skin and DNA repair, the effect of KDM1A inhibition on cellular ultraviolet (UV) response has not been studied. The ability of KDM1A inhibitor bizine to modify cell death after UVA and UVB exposure was tested in normal human keratinocytes and melanocytes, HaCaT, and FaDu cell lines. KDM1A was also downregulated using shRNA and inhibited by phenelzine in HaCaT and FaDu cells to confirm the role of KDM1A in UVA response. In addition, cellular reactive oxygen species (ROS) changes were assessed by a lipid-soluble fluorescent indicator of lipid oxidation, and ROS-related gene regulation using qPCR. During photodynamic therapy (PDT) studies HaCaT and FaDu cells were treated with aminolaevulinic acid (5-ALA) or HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) sodium and irradiated with 0-8J/cm2 red LED light. KDM1A inhibition sensitized cells to UVA radiation-induced cell death but not to UVB. KDM1A inhibition increased ROS generation as detected by increased lipid peroxidation and the upregulation of ROS-responsive genes. The effectiveness of both ALA and HPPH PDT significantly improved in vitro in HaCaT and FaDu cells after KDM1A inhibition. KDM1A is a regulator of cellular UV response and KDM1A inhibition can improve PDT efficacy.