Although surgery is the primary method to treat malignant melanoma, it has drawbacks such as residual tumor that could trigger cancer recurrence and wound infections that are especially difficult to heal in diabetics. In this research, we have constructed anti-cancer peptides/polyvinyl alcohol (PVA) double-network (DN) hydrogels for the treatment of melanoma. The maximum stress of the DN hydrogels is found to be larger than 2 MPa, which endows the DN hydrogels with ideal mechanical performance for therapeutic wound dressing. The peptides naphthalene-FIIIKKK (IK1) and phloretic acid-FIIIKKK (IK3) that were previously developed as effective antibacterial peptides, as well as the peptide/PVA DN hydrogels, are found to have good anti-cancer efficacy and target mouse melanoma cells B16-F10 while being nontoxic to normal cells. Further studies have revealed that IK1 and IK3 damage the tumor cell membrane and mitochondrial membrane and eventually trigger apoptosis. In the mouse melanoma model and the diabetic bacterial infection model, the DN hydrogels exhibit great anti-tumor, anti-bacterial, and wound healing promotion abilities in vivo. Because of their excellent mechanical properties, the DN hydrogels are promising soft materials for directly treating malignant melanomas as well as for preventing recurrence and bacterial infection after melanoma surgery that promote wound healing.

T cell immunoglobulin and mucin domain-containing-3 (TIM-3) is an immune checkpoint expressed mainly on CD4+ and CD8+ T cells. In addition to negatively regulating inflammatory T cell function, TIM-3 is a promising immunotherapy target. Herein, the aim is to develop an immuno-positron emission tomography (immunoPET) probe for noninvasively characterizing TIM-3 expression. Flow cytometry is used to detect the expression levels of TIM-3 in B16F10 cells. RMT3-23, a rat antimouse TIM-3-specific monoclonal antibody, is radiolabeled with 64Cu and the performance of 64Cu-NOTA-RMT3-23 is interrogated by immunoPET in murine melanoma models before and after radiation therapies. Biodistribution and immunofluorescent staining studies are carried out after the immunoPET imaging studies. TIM-3 is negatively expressed in B16F10 cells, and its expression is not induced by radiation therapies. ImmunoPET imaging with 64Cu-NOTA-RMT3-23 precisely tracks the unique distribution of TIM-3-positive lymphocytes in immunocompetent melanoma models, and tumor uptake of the radiotracer is not affected by either single-dose or fractionated radiation therapies. The 64Cu-NOTA-RMT3-23 immunoPET imaging results are further mirrored by the immunofluorescent staining studies. These results demonstrate the feasibility of 64Cu-NOTA-RMT3-23 immunoPET in tracking TIM-3 and highlight a new opportunity to optimize TIM-3-targeted immunotherapies with this novel imaging strategy.

As an analytic tool in medicine, deep learning has gained great attention and opened new ways for disease diagnosis. Recent studies validate the effectiveness of deep learning algorithms for binary classification of skin lesions (i.e., melanomas and nevi classes) with dermoscopic images. Nonetheless, those binary classification methods cannot be applied to the general clinical situation of skin cancer screening in which multi-class classification must be taken into account. The main objective of this research is to develop, implement, and calibrate an advanced deep learning model in the context of automated multi-class classification of skin lesions. The proposed Deep Convolutional Neural Network (DCNN) model is carefully designed with several layers, and multiple filter sizes, but fewer filters and parameters to improve efficacy and performance. Dermoscopic images are acquired from the International Skin Imaging Collaboration databases (ISIC-17, ISIC-18, and ISIC-19) for experiments. The experimental results of the proposed DCNN approach are presented in terms of precision, sensitivity, specificity, and other metrics. Specifically, it attains 94 % precision, 93 % sensitivity, and 91 % specificity in ISIC-17. It is demonstrated by the experimental results that this proposed DCNN approach outperforms state-of-the-art algorithms, exhibiting 0.964 area under the receiver operating characteristics (AUROC) in ISIC-17 for the classification of skin lesions and can be used to assist dermatologists in classifying skin lesions. As a result, this proposed approach provides a novel and feasible way for automating and expediting the skin lesion classification task as well as saving effort, time, and human life.

Rationale: Mutations in KIT, a major cancer driver gene, are now considered as important drug targets for the treatment of melanomas arising from mucosal and acral tissues and from chronically sun-damaged sites. At present, imatinib is the only targeted drug for KIT-mutation-bearing melanomas that is recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice guidelines. Patients with KIT mutations, however, are either insensitive or rapidly progress to imatinib insensitivity, which restricts its clinical use. Thus, effective inhibitors of KIT-mutation-bearing melanomas are urgently needed. Methods: A cohort of patient-derived tumor xenograft (PDX) models and corresponding PDX-derived cells (PDCs) from patients with melanomas harboring KIT mutations (KIT V560D, KIT K642E and KIT D816V) were established, characterized, and then used to test the in vitro and, subsequently, in vivo inhibitory effects of a panel of known KIT inhibitors. Results: Ponatinib was more potent than imatinib against cells bearing KIT mutations. In vivo drug efficacy evaluation experiments showed that ponatinib treatment caused much stronger inhibition of KIT-mutation-bearing melanomas than did imatinib. Mechanistically, molecular dynamics (MD) simulations revealed a plausible atomic-level explanation for the observation that ponatinib has a higher affinity for the KIT D816V mutant protein than does imatinib. Conclusions: Our study of KIT-mutation-and KIT WT-bearing melanomas demonstrates that ponatinib is a far more potent inhibitor than is imatinib for KIT-mutation-bearing melanomas and thus underscores that ponatinib should be given priority consideration for the design of precision treatments for melanoma patients triaged to have KIT mutations. Moreover, our work provides a rationale for undertaking clinical trials to examine the repurposing of ponatinib, which is already approved for use in leukemia, for use in treating a large subset of melanoma patients.

Boron neutron capture therapy (BNCT) is a binary therapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope boron-10 is irradiated with neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. In this Commentary we will focus on a number of papers that were presented at a Symposium entitled \"Current Clinical Status of Boron Neutron Capture Therapy and Paths to the Future\", which was held in September 2017 at the China National Convention Center in Beijing. Results were presented by clinicians from Japan, Finland, the United States, the China mainland and Taiwan, China who have been working in the multiple disciplines that are required for carrying out clinical BNCT. The main focus was on the treatment of patients with malignant brain tumors, recurrent tumors of the head and neck region, and cutaneous melanomas. The results obtained in treating these patients were reported in detail and, although most of the patients with brain tumors and head and neck cancer were not cured, there was evidence of some clinical efficacy. Although there are a number of problems that must be addressed, further clinical studies to evaluate the efficacy of BNCT are warranted. First, despite considerable effort by numerous investigators over the past 40 years, there still are only two boron-containing drugs in clinical use, L-boronophenylalanine (BPA) and sodium borocaptate (BSH). Therefore, until new and more effective boron delivery agents are developed, efforts should be directed to improving the dosing and delivery of BPA and BSH. Second, due to a variety of reasons, nuclear reactor-based BNCT has ended except for its use in the China mainland and Taiwan. Therefore, the future of BNCT depends upon the results of the ongoing Phase II clinical trials that are being carried out in Japan and the soon to be initiated trials that will be carried out in Finland. If the results obtained from these clinical trials are sufficiently promising, then BNCT will have a clear path to the future, especially for patients with the therapeutically challenging malignancies that in the past have been treated with reactor-based BNCT.

Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

BRAF gene mutation is found in more than 60% of malignant melanomas, which are difficult to treat. In this study, a new tumor-targeting liposome was developed to deliver anti-BRAF siRNA (siBraf) for the treatment of melanomas. Nucleolin is overexpressed on the surface of cancer cells. AS1411, an aptamer showing specific binding to nucleolin, was conjugated to PEGylated cationic liposome as the targeting probe ASLP (AS1411-PEG-liposome). The ASLP/siRNA complex was formed through electrostatic interaction between ASLP and siRNA. The binding of AS1411 to the surface of PEGylated liposomes was confirmed by gel electrophoresis and capillary electrophoresis. Real-time PCR and Western blot analysis showed that ASLP/siBraf exhibited strong silencing activity of BRAF gene. The much higher accumulation of the siRNA in tumor cells comparing with normal cells indicated that ASLP displayed excellent tumor-targeting capability. Notably, ASLP/siBraf showed significant silencing activity in A375 tumor xenograft mice and inhibited the melanoma growth. These results suggested that the new nucleolin-targeted siRNA delivery system by AS1411 may have the potential for the treatment of melanoma.