LncRNA JPX promotes tumor progression by interacting with and destabilizing YTHDF2 in cutaneous melanoma.

Aberrant long noncoding RNAs just proximal to Xist (lncRNA JPX) expression levels have been detected in multiple tumors. However, whether JPX is involved in melanoma progression remains unclear. Our study showed that JPX expression is significantly increased in melanoma tissues and cell lines. To clarify the effect of JPX on cutaneous melanoma, we successfully generated JPX-overexpressing or JPX-knockdown A375 and A2058 cells. CCK-8, colony formation, EdU, Transwell, and cell cycle phase assays were performed, and subcutaneously implanted tumor models were used to determine the function of JPX in cutaneous melanoma. The results showed that JPX knockdown reduced the proliferation and migration of malignant melanoma cells both in vitro and in vivo. To further elucidate the molecular mechanism of JPX-induced cutaneous melanoma deterioration, we performed RNA pull-down, RIP, Co-IP, Western blot, and RNA-seq analyses. JPX can directly interact with YTHDF2 and impede the protection of YTHDF2 from ubiquitin-specific protease 10 (USP10), which promotes its deubiquitination. Thus, JPX decreases protein stability and promotes the degradation of YTHDF2, thereby stabilizing BMP2 mRNA and activating AKT phosphorylation. Overall, our study revealed a novel effect of JPX on YTHDF2 ubiquitination, suggesting the possibility of blocking the JPX/USP10/YTHDF2/BMP2 axis as a prospective therapeutic approach for cutaneous melanoma. Implications: This study highlights the ubiquitination effect of USP10 and JPX on YTHDF2 in cutaneous melanoma, and proposes that the JPX/USP10/YTHDF2/BMP2 axis may be a prospective therapeutic target for cutaneous melanoma.

Albendazole induces an anti-tumor effect and potentiates PD-L1 blockade immunotherapy.

BACKGROUND: Previously, albendazole (ABZ) has been reported as an anti-parasitic drug rather than anti-tumor drug. Our study aim to investigate whether ABZ also has a potential anti-tumor effect by shaping the tumor immune microenvironment and interrogate whether ABZ could synergize with the PD-L1 blockade. METHODS: C57BL/6 mice (C57) were intravenously injected with B16F10-luciferase (B16-luc) cells to establish a lung metastatic melanoma model and subcutaneously inoculated with B16-luc cells to establish a subcutaneous tumor model. The tumor volume and tumor metastasis loci of the mice were measured by a vernier caliper and in vivo imaging. RNA sequencing was performed to analyze the different genes and pathways of immune cells in the tumors. Flow cytometry and immunofluorescence were used to analyze the different subsets of tumor-infiltrating immune cells. RESULTS: The results suggested that ABZ significantly inhibited lung melanoma metastasis with decreased fluorescence intensity and nodule score and mediated the regression of subcutaneous melanoma in mice with decreased tumor volume. Moreover, RNA sequencing results showed that ABZ regulated the gene expression levels and pathways of immune cells in the tumor microenvironment (TME). Meanwhile, flow cytometry and immunofluorescence showed that the number and percentage of CD8+ T cells, CD4+ T cells, and TH1 cells were enhanced in tumors after ABZ treatment. Furthermore, the combination of ABZ and anti-PD-L1 treatment significantly potentiated anti-tumor efficacy in both lung metastasis and subcutaneous melanoma models and mediated an increase in the percentage of CD8+ T cells, CD4+ T cells, and TH1 cells as compared to the control group. CONCLUSION: ABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression.

The Role of Photodynamic Therapy in Triggering Cell Death and Facilitating Antitumor Immunology.

Cancer is a major threat to human health because of its high mortality, easy recurrence, strong invasion, and metastasis. Photodynamic therapy (PDT) is a promising minimally invasive treatment for tumor. Compared with traditional treatment methods, PDT is less invasive and does not easily damage normal tissues. Most of the effects of this treatment are due to the direct effects of singlet oxygen together with reactive oxygen species. PDT can provide the source of active oxygen for the Fenton reaction, which enhances ferroptosis and also improves the efficacy of PDT in antitumor therapy. Additionally, in contrast to chemotherapy and radiotherapy, PDT has the effect of stimulating the immune response, which can effectively induce immunogenic cell death (ICD) and stimulate immunity. PDT is an ideal minimally invasive treatment method for tumors. In this paper, according to the characteristics of anti-tumor immunity of PDT, some tumor treatment strategies of PDT combined with anti-tumor immunotherapy are reviewed.

Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3ß/Tyr216 Accumulation.

Albendazole (ABZ) is an effective broad-spectrum anthelmintic agent that has been widely used for humans and animals. Previous studies have reported that ABZ exhibits antitumor effects against melanoma and other different cancer types; however, it is unknown whether ABZ exerts the inhibitory effect against melanoma metastasis. In this study, we aimed to investigate the inhibitory effect of ABZ on melanoma cells. Through in vitro studies, we discovered that low-dose ABZ treatment significantly inhibited the migration and invasion, but not the proliferation, of A375 and B16-F10 cells in a dose-dependent manner. Further analysis revealed that ABZ treatment reduced the expression level of snail family transcriptional repressor 1 (Snail) in the cytoplasm and nucleus by decreasing the levels of phosphorylated AKT (pAKT) Ser473/GSK-3ß (pGSK-3ß) Ser9 and increasing pGSK-3ß/Tyr216, resulting in a significant upregulation of E-cadherin and downregulation of N-cadherin and ultimately reversing the epithelial-mesenchymal transition (EMT) process of melanoma cells. In contrast, the continuous activation of AKT via transfected plasmids elevated the protein levels of pAKT Ser473/pGSK-3ß Ser9 and Snail and antagonized the inhibitory action of ABZ. We also confirmed that ABZ treatment effectively inhibited the lung metastasis of melanoma in nude mice in vivo. Subsequent immunohistochemical analysis verified the decreased pAKT Ser473/pGSK-3ß Ser9 and increased pGSK-3ß/Tyr216 levels in ABZ-treated subcutaneous tumors. Therefore, our findings demonstrate that ABZ treatment can suppress the EMT progress of melanoma by increasing the pGSK-3ß/Tyr216-mediated degradation of Snail, which may be used as a potential treatment strategy for metastatic melanoma.

Susceptibility and Resistance Mechanisms During Photodynamic Therapy of Melanoma.

Melanoma is the most aggressive malignant skin tumor and arises from melanocytes. The resistance of melanoma cells to various treatments results in rapid tumor growth and high mortality. As a local therapeutic modality, photodynamic therapy has been successfully applied for clinical treatment of skin diseases. Photodynamic therapy is a relatively new treatment method for various types of malignant tumors in humans and, compared to conventional treatment methods, has fewer side effects, and is more accurate and non-invasive. Although several in vivo and in vitro studies have shown encouraging results regarding the potential benefits of photodynamic therapy as an adjuvant treatment for melanoma, its clinical application remains limited owing to its relative inefficiency. This review article discusses the use of photodynamic therapy in melanoma treatment as well as the latest progress made in deciphering the mechanism of tolerance. Lastly, potential targets are identified that may improve photodynamic therapy against melanoma cells.

Nontuberculous Mycobacteria Infection After Autologous Fat Grafting for Cosmetic Breast Augmentation.

BACKGROUND: Autologous fat grafting has been widely applied in cosmetic breast augmentation in recent years. However, nontuberculous mycobacteria infection, as one of the multiple complications described in the literature, has been less well discussed. OBJECTIVE: The aims of the study were to report 5 cases of nontuberculous mycobacteria infection after autologous fat injection for the cosmetic breast augmentation and to explore its causes. METHODS: In this noncomparative, retrospective, and interventional case series, we identified 5 patients with nontuberculous mycobacteria infection. All patients had a history of previous autologous fat injection into the breast for cosmetic purpose, performed in different plastic facilities. RESULTS: Five patients developed nontuberculous mycobacteria infection after autologous fat injection for cosmetic breast augmentation and came to our group for treatment. Grafted fat removal through multiple debridement and long-term intravenous and oral antibiotic therapy were required in our cases. CONCLUSIONS: The number of nontuberculous mycobacteria infection after autologous fat injection into the breast is increasing. Surgeons should be aware of the complication, which rarely manifests during the procedure itself. Strict aseptic principles should be obeyed throughout the surgery.

Ocular preservation through limited tumor excision combined with ALA-PDT in patients with periocular basal cell carcinoma.

BACKGROUND: In recent years, photodynamic therapy (PDT) has emerged as a successful technique for treating early non-melanoma skin cancers compared with traditional methods such as surgical operation, chemotherapy, radiotherapy, and immunity treatment, etc. PDT offers excellent aesthetic results and skin function preservation effects, especially so for tumor in difficult-to-treat areas. The purpose of this article was to study the anti-tumor effect of ALA-PDT combined with limited excision in periocular basal cell carcinoma (BCC) and its role in improving the effect of the operation. METHODS: In our study, 8 patients with periocular basal cell carcinoma were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with surgery. After removal of tumor mainly with normal tissue saved, each tumor region was irradiated with 177 J/cm2 using a 635-nm laser for 15 min. A total of 3 times of assisted ALA-PDT was applied during and after operation. BCC was confirmed by pathological examination and the structure of tumor tissues was observed by transmission electron microscopy. RESULTS: Transmission electron microscopy showed that PDT had inhibitory effects on the growth of BCC by causing necrosis of tumor cells. There was no recurrence in the follow-up of 2.8 years (range, 0.6-5 years). The patients with infiltrative orbital BCC were able to complete the treatment protocol with good cosmetic results and no significant side effects. CONCLUSIONS: PDT in combination with limited surgery is a safe, effective and minimally-invasive approach for treating orbital BCC. Topical PDT during and after operation can reduce the excision range of the tumor lesions. Therefore, PDT may play a positive role in the treatment of periocular basal cell carcinoma.

Treatment of verrucous carcinoma in penis with topical aminolevulinic acid photodynamic therapy: An effective and safe treatment method.

BACKGROUND: Verrucous carcinoma of the penis is a rare disease characterized by verrucous lesions. The traditional treatment methods for verrucous carcinoma result in loss of sexual function are not satisfactory. The purpose of this study was to evaluate the safety and effect of topical aminolevulinic acid photodynamic therapy in the treatment of verrucous carcinoma in penis. MATERIALS AND METHODS: In this study, four male patients, average age of (47 ± 7.58) years old, with penile verrucous carcinoma were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the lesions were removed under local anesthesia. Then, the first session of PDT was performed right away. Ten percent 5-ALA cream was applied to surface of the lesions with occlusive dressing for a 3-h incubation period and the lesions were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm2 intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary. RESULTS: Three patients were cured by this treatment, with one case relapsed at 3 months. There was no other recurrence at 5 years off treatments. The satisfaction rate of patients was 75% at 3 months after treatments. CONCLUSIONS: Topical PDT can be an effective and successful treatment modality for verrucous carcinoma in penis.