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We report a case of nodular melanoma. A 46-year-old female presented with a brown papule on the medial side of the right upper arm for more than 40 years, with an increase in size for 2 months. Dermatological examination revealed a demarcated brown fungoid nodule with crusts, 1.3 cm in diameter, on the medial side of the right upper arm. The nodule was surrounded by light erythema, without ulceration. Histopathology showed exophytic nodular growth, involving both the epidermis (Paget's cells) and the reticular dermis. The tumor cells appeared in epithelioid or spindle shapes with abundant cytoplasm, vesicular nuclei of varying sizes, prominent nucleoli, and mitoses (4/HP), arranged in a nest pattern. Breslow thickness was 10 mm, and Clark level was Ⅳ. Immunohistochemistry demonstrated S-100 (diffuse+), Melan-A(+), HMB-45 (focal+), Ki-67 hot spot area(25%+), SOX-10 (diffuse+), and PRAME (diffuse+).The diagnosis of nodular melanoma was made. The patient underwent an extensive excision. The patient was recommended to seek medical care in other facility. The latest follow-up showed that surgery and chemotherapy were not given after evaluation by the oncology department at other hospital.

Objective To investigate the effect of platelet-derived growth factor (PDGF) on the activity and invasion ability of choroidal melanoma (CM) cells. Methods CM cells were divided into groups A and B and were transfected with empty vector and PDGF knockdown lentivirus, respectively. RT-qPCR was used to measure the relative expression level of PDGF mRNA; XTT assay was used to measure cell activity; Transwell assay was used to test the invasion ability of cells in the two groups; Western blot was used to measure the relative expression levels of epithelial-mesenchymal transition (EMT) marker proteins and matrix metalloproteinases (MMPs). GEPIA database was used to investigate the association between PDGF and the prognosis of CM patients. Results Compared with group A, group B had significant reductions in the relative expression level of PDGF RNA (t=176.30,P

Objective To study the relative expression and function of the nuclear transcription factor ZNF407 in melanoma and its influence and mechanism on the migration and invasion. Methods From January 2015 to January 2021, 42 cases of cutaneous malig- nant melanoma and 20 eases of pigmented nevus in Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital were collected. We examined the expression of ZNF407 in melanoma cell lines and tissues through semi-quantitative polymerase chain Reaction (qRT-PCR) and westernblot. Pearson correlation analysis detection was used to analysis mRNA expression of ZNF407 and TGF-B-1. Melanoma cell line A375 was set as target cells, pcDNA3.1 (+) Flag-ZNF407 (experimental group) and pcDNA3.1 (+)-Flag-Vector (negative control group) were transfected, respectively. The non transfected group was the set as blank control group. Transwell assay was used to detect the effects of celluar migration and invasion; the effects of ZNF407 on the expression levels of epithelial mesenchymal transition (EMT) related mRNA were detected by semi quantitative PCR and real-time quantitative PCR. Westernblots were used to ex- plore the mechanisms of ZNF407 in epithelial-mesenchymal transition and the mechanisms of ZNF407 on TGF/B signaling pathway. Results ZNF407 protein and mRNA were downregulated in human malignant melanoma tissues compared with normal tissues and its mRNA was down-regulated in melanoma cell lines (P < 0.001) Compared with the control group, transwell migration assay showed that the number of cells in the ZNF407 group (116±17) was lower than that in the control group (265±27, P<0.01) and blank control group (259 ± 28, P < 0.01 ) . Transwell invasion assay showed: The number of invated cells in the experimental group (82 ± 14) was lower than that in the control group (215±31, P<0.01) and blank control group (209 ± 32, P<0.01). Westernblot showed that overexpression of ZNF407 resulted in downregulation of protein expression of Vimentin, N-cadherin, Twist, and MMP7; The protein expression of E-cadherin was upregulated (P < 0.001) ; RT-PCR and qRT-PCR showed that over-expression of ZNF407 mRNA resulted in downregulation of stem cell markers ABCG2, Snail2, and OCT4 mRNA expression in the experimental group (P < 0.001) Correlation analysis showed that ZNF407 and TGF-β1 mRNA expression was negatively correlated in melanoma tissues ( P = 0.033, r = - 0.714 ). And over-expressed of ZNF407 inhibited cell migration and invation by downregulating of TGF-β-1 pathways and its downstream target proteins p-Smad1, p-Smad2, p-Smad3, p-Smad4 and c-Myc. Conclusion The expression of ZNF407 protein and mRNA was down-regulated in melanoma, over-expressed of ZNF407 expression could inhibit the cell migration and invasion of melanoma cell lines. Overexpression of ZNF407 could inhibit the ex- pression of TGF-β/Smad signal and its downstream of the pathway, and it could be acted as an important tumor suppressor gene in primary melanoma. [ABSTRACT FROM AUTHOR]

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Objective To investigate the clinical features of malignant melanoma of nasal cavity and paranasal sinuses (sinonasal malignant melanoma, SNMM) and its correlation with prognosis. Methods A retrospective analysis was conducted on 30 cases of SNMM treated at the Second Hospital of Lanzhou University from July 2010 to March 2024. Kaplan-Meier method and Cox regression model were used for survival analysis to identify factors affecting patient prognosis.Results Among the 30 patients,15 were males and 15 were females,aged between 38 and 81 years with an average age of 60.37 years.Survival time ranged from 1 to 89 months,with a 1-year survival rate of 81.00%, 3-year survival rate of 54.09%, and 5-year survival rate of 37.86%.The median survival time was 28.13 months. Kaplan-Meier method suggested that age, time from initial symptoms to diagnosis, primary tumor site, orbital involvement, Ki-67 expression levels, tumor staging and treatment were associated with survival rates.Tumor staging was identified as an independent factor affecting the survival rate in SNMM patients. Conclusion SNMM has high malignancy and poor prognosis, with regular postoperative followup being critical to improving survival rates. Current treatment mainly consists of a combination of surgery,postoperative radiotherapy,chemotherapy,immunotherapy and biotherapy.

Background and purpose: Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma. High mobility group A2 (HMGA2) has been proven to play an important role in the occurrence and development of various tumors, but its biological functions in leptomeningeal metastatic melanoma cells remain unclear. On the basis of building mouse models of central nervous system metastasis of melanoma, this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells, primary site melanoma cells and brain parenchymal metastatic melanoma cells, and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells. Methods: B16 mouse melanoma cells (B16-parental cells, B16-Par) stably expressing tdTomato and luciferase were generated by lentiviral infection. Subsequently, B16 specific brain parenchymal metastatic cells (B16-brain metastatic cells, B16-BrM) and B16 specific leptomeningeal metastatic cells (B16-leptomeningeal metastatic cells, B16-LM) were collected after adaptive screening of metastatic sites in vivo. The differences in migration and proliferation among B16-Par, B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8 (CCK-8). RNA sequencing (RNA-seq) was used to analyze differential gene expression in B16-Par, B16-BrM and B16-LM, and HMGA2 gene specifically upregulated in B16-LM was screened out. The results were verified by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Gene ontology (GO) analysis was performed for genes which were upregulated in B16-LM specifically. siRNA was used to interfere with the expression of HMGA2 gene in B16-LM, and the knock-down effect was verified by RTFQ-PCR and Western blot. The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay. Using GSE174401 data in Gene Expression Omnibus (GEO), the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified. Results: Compared with Par cells, tumor cells screened by the brain environment were more likely to colonize the central nervous system. B16-LM had stronger migration and proliferation abilities, and upregulated the expression of HMGA2 gene. GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation. When the expression of HMGA2 gene was knocked down, the migration and proliferation of B16-LM could be inhibited. HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients. Conclusion: Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics, which promoted cell migration and proliferation by upregulating HMGA2 gene expression.

Objective To explore the effect of PRKCH on CD8+T cell function and its role in predicting the efficacy of melanoma immunotherapy. Methods Kaplan-Meier survival analysis was used to evaluate the correlation between PRKCH and overall survival (OS) in melanoma immunotherapy cohorts and The Cancer Genome Atlas (TCGA) data. Single-cell RNA-sequencing (scRNA-seq) data were employed to analyze the cellular expression of PRKCH. Protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were applied to analyze the mechanism of PRKCH-induced anti-tumor immune responses. After retroviral overexpression and knockdown of PRKCH, the function of mouse CD8+T cells was examined. The anti-tumor effect of PRKCH overexpressed OT-1 CD8+T cells was assessed using B16-OVA mouse melanoma model. Results A positive correlation was observed between PRKCH expression and OS in the melanoma ICI cohorts and SKCM data in TCGA. scRNA-seq data indicated that PRKCH was expressed in T cells. PPI, GSEA and scRNA-seq data showed that PRKCH may induce more cytotoxic and memory T cells. PRKCH overexpression and knockdown enhanced and decreased CD8+T cell proliferation and IFN-γ and Granzyme B expression, respectively. Additionally, PRKCH overexpression enhanced the tumor inhibition of OT-1 CD8+T cells. Conclusion PRKCH enhances the anti-tumor effect of CD8+T cells, and can be used to predict the efficacy of immunotherapy in melanoma.

Immune checkpoint inhibitors have significantly improved the prognosis of patients with melanoma, but primary and acquired resistance have led to a bottleneck in treatment. The binding of T-cell receptors to tumor antigens is the key point for immunotherapy. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations. Neoantigens, identifiable as foreign entities, have the capacity to initiate an immune response unfettered by central and peripheral tolerance mechanisms. This distinctive characteristic renders them highly promising targets in the realm of cancer therapy. Vaccines targeting tumor neoantigens, adoptive cell transfer, and antibody-based therapies can effectively enhance and expand tumor-specific immune responses, promoting T-cell recognition and elimination of tumors, thereby breaking through current treatment bottlenecks. This article discusses the current status, recent advancements, clinical challenges, and future directions in the personalized treatment of melanoma based on neoantigens. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy and safety of PD-1 antibody versus high-dose interferon in the adjuvant treatment of stage IIB-IIID melanoma patients after surgery. Methods: Clinical data of patients with stage IIB-IIID cutaneous and acral melanoma admitted into Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School between September 2013 and September 2022 were retrospectively collected. All patients received high-dose interferon (HDI) or PD-1 antibody as adjuvant therapy after surgery. Univariate survival analysis was performed and survival curves were plotted by the Kaplan-Meier method; Log-Rank method was used to analyze and assess whether the differences in RFS, DMFS, and OS between the groups were statistically significant, and prognostic factors were evaluated by univariate and multivariate Cox regression. Results: A total of 91 patients were enrolled in this study with a median follow-up of 31.0 months. The median RFS was 29.2 and 32.3 months in the HDI group and the PD-1 antibody group, respectively, and the difference was not statistically significant (HR=0.90, 95%CI [0.50, 1.64]; P=0.736). The median DMFS and the median OS in the HDI group were 36.0 and 109.2 months respectively, and neither was reached in the PD-1 antibody group (both P>0.05). The most common site of first distant metastasis in both groups was the lung, and there was no statistically significant difference in the incidence of distant metastasis at any site (P>0.05). By univariate Cox analysis, compared with PD-1, antibody HDI reduced the risk of distant metastasis in patients with BRAFV600E/K mutations (HR=10.03, 95% CI [1.10, 91.35]; P=0.041). Subgroup analyses showed that in patients with cutaneous and acral melanoma, the difference in RFS between the HDI group and the PD-1 antibody group was not statistically significant (both P>0.05). The incidence of adverse reactions in the HDI group and the PD-1 antibody group was 83.3% and 79.1%, respectively, most of which were grade 1 or 2. No deaths related to adverse reactions occurred in both groups. Conclusion: In this study, there was no statistically significant difference in clinical efficacy and safety between PD-1 antibody and HDI adjuvant therapy for malignant melanoma patients. Patients with BRAFV600E/K mutations may benefit more from HDI. Numerous prospective studies are needed to further explore the optimal adjuvant treatment options for melanoma patients in Asian populations. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of midchain fatty acid decanoic acid on CD8+ T cell activation and its effect and mechanism in CD8+ T cell-mediated anti-tumor immune response. Methods: Subcutaneous melanoma B16F10 cells tumor-bearing C57BL/6 mouse models were established and randomly divided into the decanoic acid group (10 mg/kg decanoic acid by gavage) and the control group (equal amount of solvent by gavage). The effect of decanoic acid on the growth of mouse tumors and their survival rate were measured. The activation of tumor-infiltrated CD8+ T cells in the tumor microenvironment was detected by flow cytometry. The α-CD8 mAb was used to deplete CD8+ T cells in B16F10 tumor-bearing mice, and the effect on the tumor volume was observed. Mouse primary CD8+ T cells were treated with decanoic acid, and T cell receptor (TCR) activation, effector cytokine production as well as proliferation and metabolism levels were detected by WB, ELISA, qPCR, and flow cytometry. In B16F10 tumor-bearing mouse model, the effects of administration of α-PD-1 mAb combined with decanoic acid on the growth of mouse tumors and mouse survival rate were observed. Results: In the mouse melanoma model, compared with those in the control group the volume of mouse transplanted tumors significantly reduced and mouse survival rate significantly increased in the decanoic acid group. (both P<0.05). The expression levels of IFN-γ and TNF-α in tumor-infiltrating CD8+ T cells were significantly higher in the decanoic acid group than that in the control group (P<0.01). The killing ability of OT-I T cells against B16F10-OVA cells was significantly elevated after treatment with decanoic acid (P<0.01). The suppressive effect of decanoic acid on transplanted tumors was significantly reduced after CD8+ T cells were depleted with α-CD8 mAb in the melanoma mouse model (P<0.000 1). Mouse-derived primary CD8+ T cells treated with decanoic acid showed significantly higher levels of TCR activation, increased production of cytokines IL-2 and IFN-γ, and significantly up-regulated the mitochondrial metabolic level (all P<0.05). In the melanoma mouse model, decanoic acid in combination with α-PD-1 mAb significantly inhibited tumor growth and increased the survival rate (both P<0.05). Conclusion: Decanoic acid can enhance the anti-tumor immune responses by promoting CD8+ T cell activation. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of anti-neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors (ICI-PNS). Methods and Results A total of 5 patients with anti-neuronal antibody positive ICI-PNS in Peking Union Medical College Hospital from January 2012 to March 2024 were included. Tumor types included small cell lung cancer (2 cases), malignant melanoma (one case), Hodgkin lymphoma (one case) and cervical cancer (one case). Immune checkpoint inhibitors (ICIs) included programmed death 1 (PD-1) inhibitors (3 cases), programmed cell death ligand 1 (PD-L1) inhibitors (one case) and bispecific PD-1/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors (one case). All 5 patients presented with high-risk neurologic phenotypes of paraneoplastic neurological syndrome (PNS), of which 4 presented with limbic encephalitis and one presented with rapidly progressive cerebellar syndrome. Anti-neuronal antibodies detected in serum and/or cerebrospinal fluid of patients included anti-Hu, γ-aminobutyric acid receptor type B (GABABR), sex-determining region of Y chromosome-related high mobility group box 1 (SOX1), metabotropic glutamate receptor 5 (mGluR5) and Yo antibodies. Neurological syndromes occurred within 2 weeks after receiving ICIs in 4 patients. The modified Rankin Score (mRS) of 4 patients was 3 at peak of illness, and one patient was 5 at peak of illness. The Common Terminology Criteria for Adverse Events (CTCAE) was grade 3 in all 5 patients. After withdrawal of ICIs and treatment with glucocorticoids and intravenous immunoglobulin (IVIg), the neurological symptoms of the patients were improved. Conclusions High/intermediate-risk anti-neuronal antibodies are diagnostic markers of ICI-PNS. Evaluation of ICI-PNS clinical phenotypes and CTCAE grading are important for immunotherapy. Discontinuation of ICIs, administration of glucocorticoids and IVIg can improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

This study focused on the effects of the differential expression of microRNA-126-3p (miR-126) on migration and invasion of human cutaneous melanoma (CM) cell line C8161, and the role of Janus tyrosine protein kinase 2/signaling and transcriptional activator 3 (JAK2/STAT3) pathway and epithelial-mesenchymal transition (EMT) process were investigated. Dysregulation of miR-126 was achieved by cell transfection, and miR-126-deregulated cells were treated with the JAK2/STAT3 pathway inhibitor AG490 or the agonist Coumermycin A1. Thus, C8161 cells were divided into 5 groups: control group (without transfection or drug treatment), negative control (NC) group (with mimics control transfection, but no drug treatment), miR-126 group (with miR-126 mimics transfection, but no drug treatment), miR-126 + pathway inhibitor group (with miR-126 mimics transfection and AG490 treatment), miR-126 + pathway agonist group (with miR-126 mimics transfection and Coumermycin A1 treatment). Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression level of miR-126. The expression levels of EMT key proteins and JAK2/STAT3 pathway proteins were determined by Western blotting. Cell viability, migration and invasion abilities were determined by cell counting kit-8 (CCK-8), scratch healing assay and Transwell chamber combined with matrix gel, respectively. Compared with the NC group, transfection with miR-126 mimics significantly increased the expression level of miR-126 in the miR-126 group (#P<0.05), while the relative cell vitality, cell migration rate and cell invasion number significantly decreased (#P<0.05), accompanied with higher protein level of E-cadherin (#P<0.05), and lower protein levels of Vimentin, N-cadherin, fibronectin (FN), JAK2, STAT3, p-JAK2, and p-STAT3, and as well as lower ratios of p-JAK2/JAK2 and p-STAT3/STAT3 (#P<0.05). More importantly, compared with NC group and miR-126 group, the above indicators of JAK2 and STAT3 protein levels were further changed in miR-126 + pathway inhibitor group (#P<0.05 and &P<0.05), whereas all the above indexes were less changed in miR-126 + pathway activator group (#P<0.05 and &P<0.05), and cell invasion number and FN, JAK2 and STAT3 protein levels in miR-126 + pathway activator group were little different from NC group without significance. Overexpression of miR-126 inhibits cell viability, migration and invasion of human CM cells presumably by blocking EMT process and inhibiting the activation of JAK2/STAT3 pathway. These results were helpful to provide a new theoretical basis for the clinical treatment of human CM and a new strategy for its treatment. [ABSTRACT FROM AUTHOR]

Background and purpose: Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma. High mobility group A2 (HMGA2) has been proven to play an important role in the occurrence and development of various tumors, but its biological functions in leptomeningeal metastatic melanoma cells remain unclear. On the basis of building mouse models of central nervous system metastasis of melanoma, this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells, primary site melanoma cells and brain parenchymal metastatic melanoma cells, and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells. Methods: B16 mouse melanoma cells (B16-parental cells, B16-Par) stably expressing tdTomato and luciferase were generated by lentiviral infection. Subsequently, B16 specific brain parenchymal metastatic cells (B16-brain metastatic cells, B16-BrM) and B16 specific leptomeningeal metastatic cells (B16-leptomeningeal metastatic cells, B16-LM) were collected after adaptive screening of metastatic sites in vivo. The differences in migration and proliferation among B16-Par, B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8 (CCK-8). RNA sequencing (RNA-seq) was used to analyze differential gene expression in B16-Par, B16-BrM and B16-LM, and HMGA2 gene specifically upregulated in B16-LM was screened out. The results were verified by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Gene ontology (GO) analysis was performed for genes which were upregulated in B16-LM specifically. siRNA was used to interfere with the expression of HMGA2 gene in B16-LM, and the knock-down effect was verified by RTFQ-PCR and Western blot. The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay. Using GSE174401 data in Gene Expression Omnibus (GEO), the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified. Results: Compared with Par cells, tumor cells screened by the brain environment were more likely to colonize the central nervous system. B16-LM had stronger migration and proliferation abilities, and upregulated the expression of HMGA2 gene. GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation. When the expression of HMGA2 gene was knocked down, the migration and proliferation of B16-LM could be inhibited. HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients. Conclusion: Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics, which promoted cell migration and proliferation by upregulating HMGA2 gene expression. [ABSTRACT FROM AUTHOR]

Autophagy is a unique biological phenomenon of eukaryotic cells. Autophagy plays a very important role in promoting the survival of cells and actively adapting to different environments. Autophagy plays a double-edged role in the development of tumor and metastasis. The research results on the link between autophagy and melanoma are inconsistent, likely due to the intrinsic heterogeneity of melanoma and the difference in methodology of detecting autophagy. However, the results of studies on different aspects support a link between autophagy and malignant melanoma, especially the important role of autophagy in targeted drug therapy. This paper reviews the dual role of autophagy in the biological processes of melanoma invasion and metastasis, in order to provide clues for the development of new therapeutic regimens and biomarkers for malignant melanoma.

Objective To explore the effect of EMT pathway on the prognosis of the patients with melanoma and the correlation between common tumor markers and EMT pathway to provide the new ideas for clinical identification and follow-up of melanoma patients with high risk of metastasis. Methods The transcriptional and clinical data of 461 melanoma patients were obtained from the TCGA database. The expression of each sample was analyzed by GSVA package with non-parametric unsupervised analysis, and the expression score of EMT pathway was obtained and divided into the low and high groups. The survival package was used for conducting the survival analysis. Then the mRNA and EMT pathway expression levels of tumor markers conducted the Spearman correlation analysis, moreover the subgroup analysis was performed according to age, sex and tumor stage. The protein expression levels of tumor markers in melanoma patients were further downloaded from the TCGA database, and the correlation analysis was also conducted to explore the correlation between the common tumor markers and EMT pathways from two perspectives of mRNA and protein expression levels. Finally, the above tumor markers, EMT pathway expression levels and clinical features were included in a multi-factor analysis to determine their impact on melanoma prognosis. Results The high expression of EMT pathway predicted the poor prognosis of melanoma patients. The mRNA expression levels of melanoma tumor markers PMEL, MLANA, TYR, and MITF were negatively correlated with the EMT pathway (P<0.05), while the mRNA expression level of MKI67 was positively correlated with the EMT pathway (P<0.05). The results of subgroup analysis of the correlation between the tumor markers and EMT pathway were basically consistent with those obtained in the total sample. High expression of tumor marker PMEL and low expression of EMT-related pathway predicted a good prognosis, while low expression of MLANA and MKI67 predicted a good prognosis when EMT-related pathway was low expression (P<0.05). The protein expression levels of PMEL, MLANA and MITF were negatively correlated with the expression of EMT pathway (P<0.05). PMEL, age and tumor stage might be the independent risk factors for melanoma prognosis. Conclusion The lower expressions of PMEL, MLANA and MITF common markers of melanoma may be related to the high expression of EMT pathway. When the EMT-related pathways are low, high expression of PMEL and MLANA and low expression of MKI67 predict a good prognosis, which should be paid a certain degree of attention to during follow-up. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of cell division cycle 25C (CDC25C) down-regulation on the mito‐ chondrial stress response and mitochondrial pathway apoptosis in melanoma B16 cells. Methods B16 cells were cul‐ tured and randomly divided into the transfection group, transfection control group and blank control group. In the transfec‐ tion group, B16 cells were transfected with the lentiviral plasmid with low-expression of CDC25C. In the transfection con‐ trol group, B16 cells were transfected with the lentiviral empty plasmid, while in the blank control group, B16 cells were cultured normally. Rhod-2/AM and MitoSOX fluorescence probe were used to detect the concentration of mitochondrial Ca2+ and mitochondrial reactive oxygen species (ROS) in B16 cells. The mRNA and protein expression levels of mitochon‐ drial stress response-related molecules mitochondrial caseinolytic protease P (ClpP) and Lon protease 1 (LONP1), as well as the mitochondrial pathway apoptosis-related molecules Caspase-9 and Caspase-3 were detected using RT-qPCR and Western blotting. Results Compared with the transfection control group and the blank control group, the concentration of mitochondrial Ca2+ and mitochondrial ROS in B16 cells increased, and the mRNA and protein expression levels of ClpP, LONP1, and Caspase-9, and Caspase-3 increased in the transfection group (P<0. 05 or P<0. 01) . Conclusion Downregulation of CDC25C in melanoma B16 cells activates the mitochondrial stress response and subsequently triggers mito‐ chondrial pathway apoptosis. [ABSTRACT FROM AUTHOR]

Oncogenic mutations are responsible for a majority of the malignancy of melanoma. Activating mutations of NRAS gene are found in 15%-20% melanoma cases, endowing the tumor cells with more aggressive phenotypes and greater difficulty to treat. The development of targeted inhibitor of mutant NRAS remains a big challenge since the mutation sites could hardly be druggable. Therefore, immune checkpoint inhibitors are currently recommended as the first-line therapy for NRAS mutant advanced melanoma albeit the response rate is still far from satisfaction. In recent years, the exploration of targeted therapy regimens has focused on the downstream pathway of NRAS, the mitogen-activated protein kinase (MAPK) pathway. A novel MEK1/2 inhibitor tunlametinib was reported to achieve an objective response rate (ORR) of 34.7% which is higher than the ORR of binimetinib in previous report. However, the phase Ⅰ trial of the pan-RAF inhibitor belvarafenib and the ERK inhibitor ulixertinib failed to show marked benefits. In the meanwhile, MEK inhibitor-based combination therapy has also achieved some progress: it was reported in the phase Ⅰb trial of the selective BRAF/CRAF inhibitor naporafenib (LXH254) combined with Trametinib in NRAS mutant melanoma that the ORR was 46.7%. The ORR of binetinib plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, ribociclib, was 32.5% in patients with NRAS mutation with concurrent alterations of CDKN2A, CDK4, or CCND1. The response rate of the combination of focal adhesion kinase (FAK) inhibitor, IN10018, and cobimetinib was 38.5%. On the other hand, only 27.2% of patients carrying NRAS mutation responded partially to the combined regimen of immune checkpoint inhibitor programmed death ligand-1 (PD-L1) monoclonal antibody durvalumab+trametinib. In addition, some preclinical findings have also shown translational potentials: for example, heat shock protein 90 (HSP90) inhibitor XL888 and serine/threonine protein kinase 19 (STK19) inhibitors were found to inhibit the growth of NRAS mutant melanoma in animal models. This article reviewed the oncogenic roles of NRAS mutation in melanoma and the cutting-edge clinical trials for the treatment of NRAS mutant melanoma, aiming to provide alterative treatment options for clinical practice and inspire novel combination regimen.

Melanoma is a highly malignant and aggressive cancer originating from melanocytes. Early diagnosis and surgical resection can achieve a good prognosis in some patients. However, metastatic progression and drug resistance are still the two major problems in the treatment of melanoma. Thus, it is necessary to elucidate the pathogenesis, new therapeutic drugs and the treatment methods. This article reviews the research progress of miRNAs in the pathogenesis of melanoma and related drugs. MiRNAs regulate the occurrence and development of melanoma mainly through MAPK, PI3K/AKT, MITF and P53 signaling pathways. Drugs targeting these pathways can achieve therapeutic benefit. MiRNAs can serve as cancer biomarkers for early detection, evaluations of prognosis and therapeutic effect. The identification and study of related miRNA-mediated signaling pathways are helpful to further elucidate the pathogenesis of melanoma and provide scientific basis for the research and development of targeted drugs.

The aim of the present study was to clarify the pathway and mechanism involved in the anti-melanona effect of Scutellarin (SCU). CCK-8 and Transwell assays were employed to evaluate the cell proliferation and migratory abilities of B16 in vitro. Then, a B16 tumor-bearing mouse model was established to explore the effect of SCU on tumor growth in vivo. Immunohistochemistry and flow cytometry were also used to examine the effect of SCU on tumor angiogenesis and the mobilization of bone marrow-derived cells, respectively. The results showed that SCU substantially decreased the proliferation of B16 cells at doses of 160, 320, and 640 μmol/L, respectively (P

Objective To explore the effects of polydopamine (PDA) plus luteolin (LUT) with photothermal therapy on tumor killing by cytotoxic lymphocytes (CTL). Methods The synthesized PDA was characterized by using a scanning electron microscope (SEM) and a contact angle analyzer. RAW264.7 cells were divided into control group, LPS group (2 μg/L), and PDA' group (50 000 μg/L). After 48 h culture, cell viability was determined by cell counting kit-8. The effect of LUT on the differentiation of RAW264.7 cells was determined by flow cytometry. Female C57BL/6 mice were randomly divided into model group, PDA group, LUT group, and PDA+LUT group. B16F10 melanoma cells were subcutaneously injected into the back of mice in each group. On the 10th day after modeling, the PDA and PDA+LUT groups received injection of PDA into the tumor as well as photothermal therapy. The mice in the four groups received injection of PBS, PDA (2.5 μg/piece), LUT (500 μg/piece), and PDA (2.5 μg/piece) plus LUT (500 μg/piece) into the muscle of the right thigh, respectively. We observed the tumor growth and survival of the model mice. On days 3 and 7 after treatment, the spleen of each mouse was taken to prepare a single cell suspension for analysis of macrophage differentiation and T cell expression by flow cytometry. Results SEM showed that the synthesized PDA had good adhesion and affinity for water. CCK8 showed that the PDA did not affect cell viability (P>0.05). Significant differences were found in the mean fluorescence intensities of CD206 and iNOS between different groups of RAW264.7 cells (F=30.72,1 516.00,P

The global incidence of melanoma increased from 2.01/ 100 000 in 1990 to 3.75/100 000 in 2019. The incidence and mortality rate of malignant melanoma in China is lower than that of the global average, but in recent years, its incidence rate has increased (3% to 5%). Malignant melanoma is the fastest growing malignant tumor in China, and new melanoma patients reach 20 000 to 30 000 cases every year. Melanoma is prone to invasion and metastasis, and the 5-year survival rate of stage IV patients is only 4.6%. Early diagnosis and treatment can greatly improve the prognosis of patients with malignant melanoma. At present, the hot spots in the diagnosis of malignant melanoma include visual aid, artificial intelligence-assisted diagnosis, histological diagnosis and differential diagnosis. Visual AIDS can be used to screen for melanoma, and dermoscopy and skin confocal technology (CT) can diagnose melanoma with sensitivity of 61% and 100%, respectively. AI based diagnosis of malignant melanoma is more accurate than that of artificial intelligence alone or doctors, and can improve the diagnosis accuracy of malignant melanoma from 55.6% to 75.0%. With the continuous progress of second-generation sequencing technology in histology diagnosis, there is still a lack of objectively and highly repeatable immunohistochemical markers applicable to all melanomas. However, with the development of melanoma genomics research, BRAF V600E and NRAS mutations have been applied in clinical diagnosis, treatment and prognosis assessment. Malignant melanoma is highly invasive, and many patients are in the advanced stage when diagnosed. Therefore, the diagnosis and treatment of melanoma in China should pay attention to the multidisciplinary diagnosis and treatment team model, and promote the diagnosis and treatment principles and guidelines based on multidisciplinary consensus.

Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. MethodsA total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients′ disease recurrence and survival were observed. ResultsAmong the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. ConclusionsIn real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy. [ABSTRACT FROM AUTHOR]

Oncogenic mutations are responsible for a majority of the malignancy of melanoma. Activating mutations of NRAS gene are found in 15%-20% melanoma cases, endowing the tumor cells with more aggressive phenotypes and greater difficulty to treat. The development of targeted inhibitor of mutant NRAS remains a big challenge since the mutation sites could hardly be druggable. Therefore, immune checkpoint inhibitors are currently recommended as the first-line therapy for NRAS mutant advanced melanoma albeit the response rate is still far from satisfaction. In recent years, the exploration of targeted therapy regimens has focused on the downstream pathway of NRAS, the mitogen-activated protein kinase (MAPK) pathway. A novel MEK1/2 inhibitor tunlametinib was reported to achieve an objective response rate (ORR) of 34.7% which is higher than the ORR of binimetinib in previous report. However, the phase Ⅰ trial of the pan-RAF inhibitor belvarafenib and the ERK inhibitor ulixertinib failed to show marked benefits. In the meanwhile, MEK inhibitor-based combination therapy has also achieved some progress: it was reported in the phase Ⅰb trial of the selective BRAF/CRAF inhibitor naporafenib (LXH254) combined with Trametinib in NRAS mutant melanoma that the ORR was 46.7%. The ORR of binetinib plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, ribociclib, was 32.5% in patients with NRAS mutation with concurrent alterations of CDKN2A, CDK4, or CCND1. The response rate of the combination of focal adhesion kinase (FAK) inhibitor, IN10018, and cobimetinib was 38.5%. On the other hand, only 27.2% of patients carrying NRAS mutation responded partially to the combined regimen of immune checkpoint inhibitor programmed death ligand-1 (PDL1) monoclonal antibody durvalumab+trametinib. In addition, some preclinical findings have also shown translational potentials: for example, heat shock protein 90 (HSP90) inhibitor XL888 and serine/threonine protein kinase 19 (STK19) inhibitors were found to inhibit the growth of NRAS mutant melanoma in animal models. This article reviewed the oncogenic roles of NRAS mutation in melanoma and the cutting-edge clinical trials for the treatment of NRAS mutant melanoma, aiming to provide alterative treatment options for clinical practice and inspire novel combination regimen. [ABSTRACT FROM AUTHOR]

Melanoma is a highly malignant and aggressive cancer originating from melanocytes. Early diagnosis and surgical resection can achieve a good prognosis in some patients. However, metastatic progression and drug resistance are still the two major problems in the treatment of melanoma. Thus, it is necessary to elucidate the pathogenesis, new therapeutic drugs and the treatment methods. This article reviews the research progress of miRNAs in the pathogenesis of melanoma and related drugs. MiRNAs regulate the occurrence and development of melanoma mainly through MAPK, PI3K/AKT, MITF and P53 signaling pathways. Drugs targeting these pathways can achieve therapeutic benefit. MiRNAs can serve as cancer biomarkers for early detection, evaluations of prognosis and therapeutic effect. The identification and study of related miRNA-mediated signaling pathways are helpful to further elucidate the pathogenesis of melanoma and provide scientific basis for the research and development of targeted drugs. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the clinical manifestations, diagnosis and treatment for recurrent primary intracranial melanoma. Methods A case of recurrent primary intracranial melanoma which confirmed by pathological examination admitted to Nantong University Affiliated Hospital in April 2022 was analyzed retrospectively, and the clinical manifestations, imaging features, pathological diagnosis and treatment methods of intracranial melanoma were summarized in combination with relevant literature. Results Total resection was performed in the first operation, and the pathological report was malignant melanoma. No radiotherapy and chemotherapy were performed after the operation. The follow-up period was more than 7 years, and there was no recurrence for 5 months after the second operation. Conclusions Long-term survival of primary intracranial melanoma is rare, and its imaging manifestations are variable, and easy to misdiagnose before surgery. Total surgical resection is the key, and aggressively repeated surgical resection remains beneficial for recurrent cases. The effect of radiotherapy and chemotherapy are uncertain. Indeed, surgery combined with stereotactic radiosurgery (SRS), targeted therapy, immunotherapy seem to be the best solution for primary intracranial melanoma. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shenyang Agricultural University is the property of Journal of Shenyang Agricultural University Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the impact of race and its interaction with clinical factors on prognosis, and to determine whether racial factor is a key prognostic factor for melanoma. Methods We examined the effect of race on survival in melanoma with the Cox proportional hazards (CoxPH) model and two machine learning methods, random forest (RF) model and gradient boosting machine (GBM) model, using the Surveillance, Epidemiology, and End Results (SEER) database. A Logistic regression model was applied to investigate the interaction effects between race and stage/ulceration factors on the melanoma-specific mortality. Results Race showed borderline significance in the Cox model and had low variable importance in two machine learning models. In the Logistic regression model, for patients diagnosed at stage Ⅰ/Ⅱ, the odds ratios (OR) of melanoma-specific mortality in non-Hispanic blacks, non-Hispanic Asians, and Hispanics were 1.76 (95%CI: 1.34-2.31), 1.52 (95%CI: 1.16-1.99) and 1.19 (95%CI: 1.04-1.35) relative to whites, while the results were not significant for patients diagnosed at stage Ⅲ/Ⅳ . Conclusion Race is not an independent prognostic factor for melanoma. It is necessary to strengthen early screening and medical interventions for melanoma patients of non-white ethnicities. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Shenzhen University Science & Engineering is the property of Editorial Department of Journal of Shenzhen University Science & Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To construct a hollow copper sulfide nano-enzyme lipid composite nanocarrier CuS@LIP, and to further investigate the effect and mechanism of CuS@LIP combined laser irradiation on killing melanoma B6-F10 cells. Methods: (2, 3-dioleoyloxy-propyl) -3-trimethylammonium-propane (chloride salt) (DOTAP) cationic liposomes (LIPs) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome-coated copper sulfide nanocarriers (CuS@LIP). The photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1 064 nm laser irradiation. The peroxidase-like activity of CuS@LIP was verified by a catalytic activity detecting system of hydrogen peroxide (H2O2) and 3, 3', 5, 5' -tetramethylbenzidine (TMB). B16-F10 cells were treated respectively with a series of mass concentration gradients of CuS or CuS@LIP with or without laser. The cell viability of B16-F10 cells was determined via CCK-8 assay. Calcein-AM/PI staining and Annexin V-FITC/PI staining combined with flow cytometry detected the effects of 20 μg/mL CuS or CuS@LIP on the cell viability and apoptosis of B16-F10 cells under laser or non-laser irradiation, respectively. Results: The average particle size of successfully prepared CuS@LIP was (178.23±6.46) nm and the average Zeta potential was (20.47±0.93) mV. The highest temperature of 80 μg/mL CuS@LIP under laser irradiation was 65.4 °C, which was higher than that of CuS at 63.4 °C. The endpoint temperature of CuS@LIP was basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP had the same peroxidase-like catalytic activity as CuS. CuS@LIP had no significant effect on the proliferation activity of B16-F10 cells in vitro when it was less than 20 μg/mL (P>0.05), but the survival rate was significantly reduced by 58.18% after laser irradiation ([29.76±3.60]% vs [87.95±8.18]%, P<0.000 1). The apoptosis rate was significantly increased ([19.34±4.41]% vs [13.36±0.86]%, P<0.01). Conclusion: The prepared CuS@LIP has physical and chemical properties, good photothermal properties and excellent peroxidase-like catalytic activity that meet the design requirements, and it shows a better effect of killing B16-F10 cells when combined with laser irradiation. [ABSTRACT FROM AUTHOR]

To clarify the anti-melanoma active extract and material basis of Veronica didyma, CCK8 method was used to evaluate the inhibitory effects of four extracts (petroleum ether extract, ethyl acetate extract, n-butanol extract, water extract), ethanol extracts and monomer compounds on the proliferation of melanoma cell lines (B16 and A375). The chemical constituents of the active fraction were systematically separated and purified by phytochemical techniques and methods. The results were as follows: (1) Ethyl acetate extract (PPNE) had a better inhibitory effect on the proliferation of B16 and A375 cells than other samples, and IC50 = 0.177 mg·mL-1 (B16), IC50 = 2.826 mg·mL-1 (A375), respectively. (2) Seven monomer compounds were obtained from PPNE were p-hydroxybenzaldehyde (1), picroside II (2), isoscutellarein 7-O-(6′″-oacetyl)-β-allopyranosyl (1′″→2″)-β-glucopyranoside (3), 3′-hydroxyl-4′-O-methylisoscutellarein 7-O-［6′″-O-acetyl-β-D-allopyranosyl-(1→2)-β-D-glucopyranoside (4), 6-O-veratroylcatalposide (5), veronicoside (6), isoscutellarein 4′-methyl ether 7-O-(6′″-O-acetyl)-ballopyranosyl (1′″→2″)-β-glucopyranoside (7). (3) Seven compounds were isolated from this plant for the first time, and HPLC showed that these seven compounds were the major components of PPNE. (4) Except Compound 1, the other six monomers all had good inhibitory effects on the proliferation of melanoma cells, and the anti-melanoma activities of compounds 3, 4 and 7 were reported for the first time. Based on these results, PPNE of V. didyma is an anti-melanoma active fraction, iridoids (compounds 2, 5, 6) and flavonoids (compounds 3, 4, 7) may be the basis of anti-melanoma activity of PPNE. The results of this study will lay scientific foundation for the rational utilization of V. didyma’s resources.

Background and purpose: Anti-programmed death-1 (anti-PD-1) adjuvant therapy and targeted therapy have resulted in longer recurrence-free survival (RFS) for malignant melanoma patients in clinical trials. However, the efficacy of adjuvant anti-PD-1 therapy in Chinese melanoma patients has not been previously reported. The purpose of this study was to retrospectively analyze the RFS in Chinese resected stage Ⅲ malignant melanoma patients treated with adjuvant anti-PD-1 therapy and to preliminarily compare it with BRAFV600 inhibitor vemurafenib. Methods: This study retrospectively collected the information of 120 patients with resected stage Ⅲ malignant melanoma from three major cancer centers in China from August 30, 2018 to August 30, 2020. These patients received adjuvant pembrolizumab/toripalimab or vemurafenib. RFS rates were assessed by Kaplan-Meier curves and log-rank tests were used to examined differences. Results: Among the 90 patients with stage Ⅲ malignant melanoma receiving adjuvant anti-PD-1 therapy, the median-RFS (mRFS) was 16 months (95% CI: 14-18 months); the 12-month RFS rate was 69.5% (95% CI: 64.6%-74.4%) and the 24-month RFS rate was 45.8% (95% CI: 40.5%-51.1%). The mRFS for 30 patients who received vemurafenib was 18 months (95% CI: 10-21 months), the 12-month RFS rate was 62.8% (95% CI: 54.0%-71.6%), and the 24-month RFS rate was 32.9% (95% CI: 27.1%-44.7%). In the stratified analysis, firstly, there was no difference in RFS between anti-PD-1 therapy group and vemurafenib group. Secondly, the BRAFV600E mutation status may did not affect the RFS of anti-PD-1 therapy. In addition, in this study, for the patients with BRAFV600E mutation, the RFS showed no difference between these patients received anti-PD-1 therapy or vemurafenib. Finally, although the RFS was better in patients with cutaneous melanoma than in patients with acral and worst in patients of unknown origin, the data for adjuvant therapy in China were still poor. Conclusion: These are the real-world data from adjuvant anti-PD-1 therapy in patients with resected stage Ⅲ cutaneous and acral melanoma patients in China. In our study, adjuvant anti-PD-1 therapy is indistinguishable from vemurafenib indicates more combination therapies are needed to improve outcome in China.

Melanoma is one of the most dangerous tumors due to its high-grade malignancy. Though patients in early stage can be completely cured by surgery, for high-risk cases (stage ⅡB-Ⅳ), adjuvant therapy is of great importance to prolong the survival and improve the prognosis. In recent years, thanks to the booming development of systemic regimen, the perioperative managements for stage Ⅲ cases have been continuously evolving. In the current paper, we focused on the role of lymph node biopsy and surgical resection, postoperative adjuvant therapy options, as well as the cutting-edge neoadjuvant therapy development, aiming to provide new perioperative strategies for stage Ⅲ melanoma patients.

Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

Objective To investigate the inhibitory effect of a natural small molecule, HEP-14, on melanoma SK-Mel-103 cells and its underlying mechanism. Methods SK-Mel-103 cells were treated with HEP-14 at different concentrations (2.5~40 μmol/L). The untreated cells were used as a control. Cell viability and colony formation were respectively assessed using CCK-8 assay and colony formation assay. Flow cytometry was applied to examine cell cycle and apoptosis. Transwell assay was used to evaluate cellular mobility. Real-time RT-qPCR was used to measure the mRNA expression of CD271 and STAT3, and Western blotting was employed to detect the protein levels of CD271, STAT3 and p-STAT3. Immunofluorescence assay was perform to confirm the expression of CD271. Results HEP-14 significantly inhibited the growth and colony formation of SK-Mel-103 cells (P < 0.05), induced cell arrest at G2/M phase (P < 0.05), promoted cell apoptosis (P < 0.05) and suppressed cell mobility in comparison with the untreated cells. In addition, HEP-14 treatment suppressed the phosphorylation of STAT3 (P < 0.05) and down-regulated the expression of CD271 (P < 0.05) in the melanoma cell lines SK-Mel-103, SK-Mel-147 and SK-Mel-28. Conclusion Natural small molecule HEP-14 effectively inhibits the proliferation and induces the apoptosis of melanoma SK-Mel-103 cells, and it suppresses the cell migration by inhibiting activation of STAT to down-regulate CD271 expression.

Death receptor pathway and perforin/granzyme pathway are the main mechanisms for immune system to kill tumor cells. SerpinB9 is the only known human protein that is able to inhibit the proteolytic activity of granzyme B (GrB). Expression of SerpinB9 has been observed in various human tumors, such as lung cancer and prostate cancer, and SerpinB9 can protect tumor cells from cytotoxic lymphocytes-mediated killing through the perforin/GrB pathway. In skin tumors, SerpinB9 expression has been detected in cells of malignant melanoma, cutaneous squamous cell carcinoma, cutaneous lymphomas, in which SerpinB9 contributes to tumor progression by mediating immune escape, resistance to immunotherapy and interference of the tumor microenvironment. In addition, researches have shown that inhibitor of SerpinB9 could retard the growth of melanoma, indicating the potential anti-tumor therapeutic application of SerpinB9 inhibition. The research status of SerpinB9 in skin tumors is reviewed in this paper.

In recent years, with more and more basic research on the POU family, it has been found that POU domain proteins are related to cell development, replication, growth, and cell cycle blocking and differentiation. POU3F2 not only participates in embryonic development and differentiation of central neuroendocrine system, but also has wide expression in malignant tumors, and regulates the proliferation, invasion and metastasis of tumor cells in different ways to affect tumor development. Based on the structure of POU3F2, the review expounds the function and research status of POU3F2 in common malignant tumors, with the hope of further studying its mechanism and preventing diseases.

Melanoma is a highly lethal skin malignant tumor. Although years of clinical studies have proved that there are various methods for its treatment, such as surgery, chemotherapy, radiotherap, targeted therapy, etc., due to its low sensitivity, strong toxic and side effects, and poor efficacy, in view of the wide application of immunotherapy in the treatment of tumor diseases, the author reviewed the progress of immunotherapy of melanoma in recent years. [ABSTRACT FROM AUTHOR]

Objective：To investigate the regulatory mechanism of long non⁃coding RNA⁃nuclear enriched transcript 1 (lnc⁃NEAT1) on the proliferation, migration and invasion of melanoma (MM) cells. Methods：MM cell lines (A375, A875, M14, B16) and human epidermal melanocytes (HEMa ⁃ LP) were cultured in vitro, real ⁃time quantitative PCR (RT ⁃ qPCR) was performed to determine the mRNA expression of lnc⁃NEAT1, microRNA⁃29c⁃3p (miR⁃29c⁃3p) and chondroitin sulfate proteoglycan 4 (CSPG4) in cells. B16 cells at logarithmic growth phase were taken and separated into control group, si⁃NC group, si⁃NEAT1 group, si⁃NEAT1+inhibitor⁃NC group, and si⁃NEAT1+miR⁃29c⁃3p inhibitor group. Lipofectamine 3000 was applied to transfect the corresponding plasmids into cells. RT⁃qPCR was performed to determine the transfection efficiency. MTT method was used to determine cell proliferation. Transwell assay was performed to determine cell migration and invasion abilities. Western blotting was performed to determine the expression of CSPG4 and proteins related to the proliferation, migration and invasion. Dual⁃luciferase reporter gene assay was performed to determine miR⁃29c⁃3p targeting relationship with lnc⁃NEAT1 and CSPG4. Nude mice xenograft experiment was performed to explore the effect of lnc⁃NEAT1 knockdown on the growth of MM cells in vivo. Results：The mRNA levels of lnc⁃NEAT1 and CSPG4 in MM cell lines were obviously higher than those in HEMa⁃LP cells, and the levels of miR⁃29c⁃3p were obviously lower than those in HEMa⁃LP cells (all P < 0.05) . Knockdown of lnc ⁃NEAT1 obviously increased miR ⁃ 29c ⁃3p expression, decreased CSPG4 mRNA and protein levels, inhibited cell proliferation, migration and invasion, and decreased Ki⁃67, N⁃cadherin and Vimentin protein levels as well as increased E⁃cadherin protein level (all P < 0.05) . Down ⁃ regulation of miR ⁃29c ⁃3p expression obviously increased CSPG4 mRNA and protein levels, and attenuated the inhibitory effects of lnc⁃NEAT1 knockdown on MM cell proliferation, migration and invasion (P < 0.05) . The results of dual⁃luciferase reporter gene assay showed that after the transfection of miR⁃29c⁃3p mimic, the luciferase activities of NEAT1⁃WT and CSPG4⁃WT in cells were obviously decreased (P < 0.05) . Nude mouse xenograft experiments showed that knockdown of lnc ⁃NEAT1 obviously inhibited the growth of xenografts in vivo, while inhibition of miR⁃29c⁃3p was able to obviously attenuate the inhibitory effect of lnc⁃NEAT1 knockdown on the growth of xenografts (all P < 0.05) . Conclusion：Lnc⁃NEAT1 may promote the proliferation, migration and invasion of MM cells by regulating the miR⁃29c⁃3p/CSPG4 axis. [ABSTRACT FROM AUTHOR]

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Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Objective To investigate the effect of Beclin1 overexpression on autophagy and EMT in melanoma A375 cells. Methods Human malignant melanoma A375 cells were divided into three groups by liposome transfection, i.e., blank group(no plasmid), NC group(transfection empty plasmid), and transfection group(transfection with Beclin1). These three groups were inoculated subcutaneously in three groups of nude mice for 21 days after tumor formation. The expression levels of mRNA and proteins, including Beclin1, LC3Ⅱ, Vimentin, N-cadherin and E-cadheirn, were detected by RT-PCR and Western blotting, respectively. Results Although tumor developed in all three groups, the tumor growth rate was significantly lower in the transfection group than in either blank or NC groups (P0.05). Compared with the blank and NC groups, the transfection group displayed significantly higher expression levels of both mRNA and proteins for Beclin1, LC3Ⅱ and E-cadherin (P

To clarify the anti-melanoma active extract and material basis of Veronica didyma, CCK8 method was used to evaluate the inhibitory effects of four extracts (petroleum ether extract, ethyl acetate extract, n-butanol extract, water extract), ethanol extracts and monomer compounds on the proliferation of melanoma cell lines (B16 and A375). The chemical constituents of the active fraction were systematically separated and purified by phytochemical techniques and methods. The results were as follows: (1) Ethyl acetate extract (PPNE) had a better inhibitory effect on the proliferation of B16 and A375 cells than other samples, and IC50 = 0.177 mg·mL-1 (B16), IC50 = 2.826 mg·mL-1 (A375), respectively. (2) Seven monomer compounds were obtained from PPNE were p-hydroxybenzaldehyde (1), picroside II (2), isoscutellarein 7-O- (6-oacetyl) -β-allopyranosyl (1→2") -β-glucopyranoside (3), 3'-hydroxyl-4'-O-methylisoscutellarein 7-O-[6-O-acetyl-β-D-allopyranosyl- (1→2) -β-D-glucopyranoside (4), 6-O-veratroylcatalposide (5), veronicoside (6), isoscutellarein 4'-methyl ether 7-O- (6-O-acetyl) -ballopyranosyl (1→2") -β-glucopyranoside (7). (3) Seven compounds were isolated from this plant for the first time, and HPLC showed that these seven compounds were the major components of PPNE. (4) Except Compound 1, the other six monomers all had good inhibitory effects on the proliferation of melanoma cells, and the anti-melanoma activities of compounds 3, 4 and 7 were reported for the first time. Based on these results, PPNE of V. didyma is an anti-melanoma active fraction, iridoids (compounds 2, 5, 6) and flavonoids (compounds 3, 4, 7) may be the basis of anti-melanoma activity of PPNE. The results of this study will lay scientific foundation for the rational utilization of V. didyma's resources. [ABSTRACT FROM AUTHOR]

Objective To construct a risk model based on m6 A methylation regulators in melanoma. To explore the value of m6 A methylation regulators in the prognosis and immunotherapy of melanoma. Methods From January 2022 to February, the data of gene expression and corresponding clinical information of 470 melanoma samples as well as sequence data of 1809 normal control samples were collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The differential expressions of 20 m6 A methylation regulators between melanoma and normal tissue was analyzed by independent t test. Based on m6 A methylation regulators, the melanoma patients were divided into two clusters by consensus clustering. The immune infiltration of two clusters was estimated by CIBERSORT. Genes significantly associated with melanoma prognosis was screened by Cox regression analysis. The risk model in melanoma was constructed by Lasso Cox regression analysis. Results There were statistical significance in difference of various m6 A methylation regulators between melanoma samples and normal samples. The ZC3H13, YTHDF3, IGF2BP2 and IGF2BP3 were remarkably up-regulated in melanoma (P<0.05). The clustering analysis and CIBERSORT analysis showed that there were differences in immune infiltration between clusters 1 and 2. Based on Lasso Cox regression analysis, RBM15B and WTAP were screened as prognostic model associated with m6 A, patients in the high-risk group had a worse prognosis (P=0.00179). Multivariate Cox regression analysis showed that RBM15B was an independent prognostic factor of melanoma. CIBERSORT analysis showed that high expression of RBM15B was associated with immune infiltration. Conclusion The m6 A methylation regulators can indicate immune infiltration in melanoma. The prognostic risk model constructed according to crucial m6A methylation regulators in melanoma has good predictive ability. RBM15B may be a potential risk factor of melanoma and potential relevant m6 A regulators of immune infiltration. This study provided new insights into the epigenetics understanding of m6A regulators and novel therapeutic strategies of melanoma. [ABSTRACT FROM AUTHOR]