AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, ...AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, surgery, and follow-up of 56 patients with anorectal melanoma who underwent surgery between 1975 and 2008 were retrospectively reviewed. The factors predictive for the survival rate of these patients were identified using multivariate analysis. RESULTS: The 5-year survival rate of the 56 patients with anorectal melanoma was 20%, 36 patients underwent abdominoperineal resection (APR) and 20 patients underwent wide local excision (WLE). The rates of local recurrence of the APR and WLE groups were 16.13% (5/36) and 68.75% (13/20), (P = 0.001), and the median survival time was 22 mo and 21 mo, respectively (P = 0.481). Univariate survival analysis demonstrated that the number of tumor and the depth of invasion had significant effects on the survival (P < 0.05). Multivariate analysis showed that the number of tumor [P = 0.017, 95% confidence interval (CI) = 1.273-11.075] and the depth of invasion (P = 0.015, 95% CI = 1.249-7.591) were independent prognostic factors influencing the survival rate. CONCLUSION: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectal melanoma.展开更多
Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led i...Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transforma-tion of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-Raf V600 E and N-RasQ 61 R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor(EGFR), stem cell-like factor(SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) and vascular endothelial growth factor(VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition(EMT)-associated molecules, including phosphatidylinositol 3'-kinase(PI3K)/Akt/ molecular target of rapamycin(mT OR), nuclear factor-kappaB(NF-κB), macrophage inhibitory cytokine-1(MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.展开更多
We read with interest the article entitled： ‘Jejuno-jejunal invagination due to intestinal melanoma’ by Resta , et al. They reported a rare clinical case of a young woman with a bleeding jejunal melanoma, whose ear...We read with interest the article entitled： ‘Jejuno-jejunal invagination due to intestinal melanoma’ by Resta , et al. They reported a rare clinical case of a young woman with a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination. The article is also referred to the rarity of gastrointestinal melanomas as well as their possible primary nature.展开更多
Melanoma of the gastrointestinal tract is a rare, highly malignant neoplasm of poor prognosis. This is description of an unusual case of surgically treated patient with two metachronous malignant melanomas of the stom...Melanoma of the gastrointestinal tract is a rare, highly malignant neoplasm of poor prognosis. This is description of an unusual case of surgically treated patient with two metachronous malignant melanomas of the stomach and the esophagus. The former lesion was located in the cardia and effectively treated with RO total gastrectomy. The latter was recognized after 67 mo and appeared as irregular, flat, pigmented areas located in the mid esophagus. Subtotal esophagectomy via right-sided thoracotomy, laparotomy and left-sided cervicotomy was performed, but neoplastic cells were found in distal margin (R1). Fourteen months after esophagectomy multiple lung metastases were detected. Patient.died 2 mo later.展开更多
BACKGROUND Anorectal melanoma (AM) is an extremely rare malignant tumor originating from anorectal melanocytes with a poor prognosis. AM has been reported to have a much lower incidence than cutaneous or choroid melan...BACKGROUND Anorectal melanoma (AM) is an extremely rare malignant tumor originating from anorectal melanocytes with a poor prognosis. AM has been reported to have a much lower incidence than cutaneous or choroid melanoma, accounting for 0.4%-1.6% of all melanomas. CASE SUMMARY We report a 76-year-old female patient diagnosed with anorectal malignant melanoma by colonoscopy and biopsy. Intraoperative examination revealed two distinct anorectal tumors, one melanotic and another amelanotic, as well as two pigmented mucosal zones at the dentate line level. Abdominal perineal resection was performed. A pathological report confirmed all four lesions to be melanomas. Postoperatively, we followed an immunotherapy protocol targeting PD-1 (nivolumab). The patient had 24 mo of disease-free follow-up upon completion of nivolumab treatment. CONCLUSION This is the first reported case presenting coexistence of pigmented and unpigmented AMs in the same patient.展开更多
AIM:To evaluate the results and complications of secondary endoresection via pars plana vitrectomy for choroidal melanoma and review the previously reported endoresection studies on the treatment of choroidal melanoma...AIM:To evaluate the results and complications of secondary endoresection via pars plana vitrectomy for choroidal melanoma and review the previously reported endoresection studies on the treatment of choroidal melanoma.METHODS:The medical records of 6 patients with choroidal melanoma who underwent secondary endoresection between March 2012 and March 2020 were retrospectively reviewed.The indications for secondary endoresection were progressive or recurrent tumor and severe exudative retinal detachment after previous treatment with plaque radiotherapy/Cyberknife radiosurgery/transpupillary thermotherapy(TTT).RESULTS:Before endoresection,2 eyes had Iodine-125 plaque radiotherapy and TTT,1 eye had Ruthenium-106 plaque radiotherapy and TTT,1 eye had Cyberknife radiosurgery and TTT,1 eye had Cyberknife radiosurgery,and 1 eye had TTT only.Preoperative visual acuity ranged from 20/63 to 20/1600(Snellen) and from 0.5 to 1.9(mean:1.1) on the log MAR scale.The mean tumor base diameters were 9.5×8.7 mm and the mean tumor thickness was 5.4 mm.After secondary endoresection,transient vitreous hemorrhage developed in 2(33.3%) eyes and retinal detachment in 1(16.7%) eye.Cytopathological examination revealed epithelioid cell melanoma in 4(66.7%) eyes and mixed cell melanoma in 1(16.7%).Melanoma cell type was not specified in 1(16.7%) eye.At a mean follow-up of 49.6 mo(range:16-90 mo),mean visual acuity did not improve and 1 eye was enucleated due to tumor recurrence.Final visual acuity ranged from 20/63 to 20/1600(Snellen) and from 0.5 to 1.9(mean:1.2) on the log MAR scale.Two patients with choroidal melanoma developed metastasis and eventually expired.CONCLUSION:Secondary endoresection seems to be an effective treatment option for globe salvage in choroidal melanoma not responsive to conventional treatment and displaying persistent exudative retinal detachment.There was no visual acuity increase among the treated eyes but globe salvage was possible in most cases in this study.展开更多
In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of oc...In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas.Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits.Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab.As a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(CMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs.Possible novel ways of treating UM are being explored.Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM.While CM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy options.Further research has to be done in order to find acceptable treatment options.展开更多
Objective:The BRAF inhibitor,vemurafenib,has been widely used in the treatment of patients with melanoma-bearing BRAFV600E mutations.While the initial response to vemurafenib is usually excellent,the majority of patie...Objective:The BRAF inhibitor,vemurafenib,has been widely used in the treatment of patients with melanoma-bearing BRAFV600E mutations.While the initial response to vemurafenib is usually excellent,the majority of patients eventually develop resistance and metastatic disease.However,the underlying molecular mechanism remains elusive.The objective of this study was therefore to identify additional molecular targets responsible for vemurafenib resistance.Methods:Western blots and immunohistochemistry analyses were used to evaluate expressions of PYK2 and p-PYK2 in cultured cells and melanoma tissue microarrays.The relationships of p-PYK2 with clinicopathological parameters were statistically analyzed.Invadopodia cell invasion,and a Ca2+assay were used to determine the effect of vemurafenib resistance-induced p-PYK2 on melanoma progression.A mouse model was used to assess the effects of PYK2 on melanoma metastasis.Results:Elevated p-PYK2 levels were detected in vemurafenib-resistant melanoma cells,and PYK2 was shown to regulate invadopodia formation in melanoma cells.Vemurafenib triggered invadopodia formation by activation of PYK2.Inhibition of PYK2 with either shRNA or the small molecule inhibitor,PF562711,dramatically reduced vemurafenib-induced invadopodia formation.Furthermore,knockdown of PYK2 significantly reduced melanoma lung metastasis in vivo.Increased expressions of p-PYK2 in melanoma patients were positively correlated with advanced stage(P=0.002),metastasis(P<0.001),and Clark grade(P<0.001),and were also associated with short overall survival[hazard ratio(HR)=3.304,P=0.007]and progression-free survival(HR=2.930,P=0.001).Conclusions:PYK2 mediated vemurafenib-induced melanoma cell migration and invasion.Inhibition of PYK2 resensitized melanoma cells to vemurafenib.Phospho-PYK2 was a prognostic biomarker in melanoma patients.展开更多
Background: The anorectal location of melanomas is extremely rare (1% - 3% of all melanomas), and the prognosis remains poor because of the aggressiveness and the high metastatic potential of those tumors. The discove...Background: The anorectal location of melanomas is extremely rare (1% - 3% of all melanomas), and the prognosis remains poor because of the aggressiveness and the high metastatic potential of those tumors. The discovery that the KIT oncogene may be aberrantly activated in a subset of patients with anorectal melanoma creates a realm of possibility for the development of targeted molecular therapy. Aim: to show the epidemiologic, clinico-radiological, histological features and treatment management especially in patients with over-expression of C-KIT treated by Imatinib. Methods: It is a retrospective study conducted in the department of medical oncology at Hassan II University Hospital between January 2007 and January 2012, including all patients with histologically proven melanoma of the anorectal area. Results: 11 cases were collected, with slight female predominance. Nine patients were metastatic at the moment of diagnosis, and only two with local stage, but evolution was marked by local and distant recurrence less than 12 months after abdo-minoperineal resection. First line of chemotherapy was based mainly on paclitaxel, carboplatine and dacarbazine. Response was modest with only 3 partial responses, 4 patients with disease stability, and 4 patients with disease progression. Two patients, with over expression of C-KIT, received Imatinib as second line of treatment with significant improvement of symptoms and radiological response reaching 50%. Seven patients died with a median survival of 11 months from diagnosis to the date of death. Conclusion: Primary anorectal melanomas are very rare, with high aggressiveness and poor prognosis. Treatment management is still a big challenge given to the modest efficacy of conventional chemotherapy. Better understanding of carcinogenesis and signaling pathways will allow development of new targeted therapies.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM...AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.展开更多
The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constrai...The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constraints of conventional drug delivery methods by their superior safety and efficacy through precise targeting,while simultaneously enabling painless delivery.Currently,MNs are increasingly used as carriers for drug delivery,with the loading of insoluble drugs to improve their treatment efficiency or combining with bioactive substances for the construction of an efficient drug delivery system to maximize the effects of bioactive substances.The methods used for preparation MNs are diverse,enabling them to meet the requirements of most applications.The emergence of MNs has addressed the shortcomings associated with insoluble drugs,expanded the applications of bioactive substances,and improved their use in clinical practice.This review summarizes current information on the application of MNs in a variety of skin diseases,such as psoriasis,vitiligo,alopecia,hypertrophic scarring,atopic dermatitis,melanoma,acne,and skin infections.The current clinical applications and future opportunities for MNs in the treatment of skin diseases are also discussed.Despite substantial progress in the clinical application of MNs as delivery vectors,issues such as low drug loading and poor mechanical strength during MNs preparation remain the main challenges.Therefore,clinical implementation of MNs-based therapies remains limited,highlighting key opportunities for future research.展开更多
Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In soli...Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In solid tumors,angiogenesis supports growth,nutrient delivery,waste removal,and metastasis.Tumors can induce angiogenesis through proangiogenic factors including VEGF,FGF-2,PDGF,angiopoietins,HGF,TNF,IL-6,SCF,tryptase,and chymase.This balance is disrupted in tumors,and extracellular vesicles(EVs)contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells(ECs).Malignant melanoma,a particular type of skin cancer,accounts for only 1%of skin cancer cases but more than 75%of deaths.Its incidence has risen significantly,with a 40%increase between 2012 and 2022,especially in fair-skinned populations.Advanced metastatic stages have a high mortality due to delayed diagnosis.This review examines the molecular basis of angiogenesis in melanoma,focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.展开更多
Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(...Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.展开更多
Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.Thi...Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.展开更多
Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ul...Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.展开更多
Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis...Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.展开更多
BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI...BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI),particularly when combined with diffusion-weighted imaging(DWI),has emerged as promising tool for comprehensive,radiation-free assessment of metastatic spread.AIM To systematically review the diagnostic performance and clinical utility of WBMRI in the staging and restaging of cutaneous melanoma,with comparison to conventional imaging modalities such as computed tomography(CT)and positron emission tomography/CT(PET/CT).METHODS A systematic literature review was conducted using PubMed,Embase,Scopus and Web of Science databases for studies published in the last 10 years.Inclusion criteria focused on comparative diagnostic accuracy studies of WB-MRI vs CT and PET/CT for melanoma staging.The methodological quality of the studies was appraised using the QUADAS-2 tool.RESULTS Sixteen studies involving over 700 patients met the inclusion criteria.WB-MRI showed high sensitivity(73%-90%)and specificity(up to 98%)in detecting metastases,particularly in bone,liver and soft tissue.DWI enhanced lesion detection,and WB-MRI often influenced clinical management decisions.However,CT outperformed WB-MRI in identifying small pulmonary nodules.AI-assisted analysis and contrastenhanced sequences further improved diagnostic confidence.CONCLUSION WB-MRI represents a robust imaging modality for staging cutaneous melanoma,offering superior soft-tissue contrast and functional imaging without ionizing radiation.Its strengths lie in detecting bone,liver and brain metastases.Challenges include limited lung lesion detection,cost,and availability.Advances in artificial intelligence,Hybrid PET/MRY systems,and radiomics are poised to expand WB-MRI’s role in personalized melanoma management.展开更多
Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the cas...Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.展开更多
文摘AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, surgery, and follow-up of 56 patients with anorectal melanoma who underwent surgery between 1975 and 2008 were retrospectively reviewed. The factors predictive for the survival rate of these patients were identified using multivariate analysis. RESULTS: The 5-year survival rate of the 56 patients with anorectal melanoma was 20%, 36 patients underwent abdominoperineal resection (APR) and 20 patients underwent wide local excision (WLE). The rates of local recurrence of the APR and WLE groups were 16.13% (5/36) and 68.75% (13/20), (P = 0.001), and the median survival time was 22 mo and 21 mo, respectively (P = 0.481). Univariate survival analysis demonstrated that the number of tumor and the depth of invasion had significant effects on the survival (P < 0.05). Multivariate analysis showed that the number of tumor [P = 0.017, 95% confidence interval (CI) = 1.273-11.075] and the depth of invasion (P = 0.015, 95% CI = 1.249-7.591) were independent prognostic factors influencing the survival rate. CONCLUSION: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectal melanoma.
基金Supported by The National Institutes of Health National Cancer Institute(Grants EDRN CA111294,and SPORE CA127297)
文摘Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transforma-tion of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-Raf V600 E and N-RasQ 61 R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor(EGFR), stem cell-like factor(SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor-4(CXCR4) and vascular endothelial growth factor(VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition(EMT)-associated molecules, including phosphatidylinositol 3'-kinase(PI3K)/Akt/ molecular target of rapamycin(mT OR), nuclear factor-kappaB(NF-κB), macrophage inhibitory cytokine-1(MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.
文摘We read with interest the article entitled： ‘Jejuno-jejunal invagination due to intestinal melanoma’ by Resta , et al. They reported a rare clinical case of a young woman with a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination. The article is also referred to the rarity of gastrointestinal melanomas as well as their possible primary nature.
文摘Melanoma of the gastrointestinal tract is a rare, highly malignant neoplasm of poor prognosis. This is description of an unusual case of surgically treated patient with two metachronous malignant melanomas of the stomach and the esophagus. The former lesion was located in the cardia and effectively treated with RO total gastrectomy. The latter was recognized after 67 mo and appeared as irregular, flat, pigmented areas located in the mid esophagus. Subtotal esophagectomy via right-sided thoracotomy, laparotomy and left-sided cervicotomy was performed, but neoplastic cells were found in distal margin (R1). Fourteen months after esophagectomy multiple lung metastases were detected. Patient.died 2 mo later.
文摘BACKGROUND Anorectal melanoma (AM) is an extremely rare malignant tumor originating from anorectal melanocytes with a poor prognosis. AM has been reported to have a much lower incidence than cutaneous or choroid melanoma, accounting for 0.4%-1.6% of all melanomas. CASE SUMMARY We report a 76-year-old female patient diagnosed with anorectal malignant melanoma by colonoscopy and biopsy. Intraoperative examination revealed two distinct anorectal tumors, one melanotic and another amelanotic, as well as two pigmented mucosal zones at the dentate line level. Abdominal perineal resection was performed. A pathological report confirmed all four lesions to be melanomas. Postoperatively, we followed an immunotherapy protocol targeting PD-1 (nivolumab). The patient had 24 mo of disease-free follow-up upon completion of nivolumab treatment. CONCLUSION This is the first reported case presenting coexistence of pigmented and unpigmented AMs in the same patient.
文摘AIM:To evaluate the results and complications of secondary endoresection via pars plana vitrectomy for choroidal melanoma and review the previously reported endoresection studies on the treatment of choroidal melanoma.METHODS:The medical records of 6 patients with choroidal melanoma who underwent secondary endoresection between March 2012 and March 2020 were retrospectively reviewed.The indications for secondary endoresection were progressive or recurrent tumor and severe exudative retinal detachment after previous treatment with plaque radiotherapy/Cyberknife radiosurgery/transpupillary thermotherapy(TTT).RESULTS:Before endoresection,2 eyes had Iodine-125 plaque radiotherapy and TTT,1 eye had Ruthenium-106 plaque radiotherapy and TTT,1 eye had Cyberknife radiosurgery and TTT,1 eye had Cyberknife radiosurgery,and 1 eye had TTT only.Preoperative visual acuity ranged from 20/63 to 20/1600(Snellen) and from 0.5 to 1.9(mean:1.1) on the log MAR scale.The mean tumor base diameters were 9.5×8.7 mm and the mean tumor thickness was 5.4 mm.After secondary endoresection,transient vitreous hemorrhage developed in 2(33.3%) eyes and retinal detachment in 1(16.7%) eye.Cytopathological examination revealed epithelioid cell melanoma in 4(66.7%) eyes and mixed cell melanoma in 1(16.7%).Melanoma cell type was not specified in 1(16.7%) eye.At a mean follow-up of 49.6 mo(range:16-90 mo),mean visual acuity did not improve and 1 eye was enucleated due to tumor recurrence.Final visual acuity ranged from 20/63 to 20/1600(Snellen) and from 0.5 to 1.9(mean:1.2) on the log MAR scale.Two patients with choroidal melanoma developed metastasis and eventually expired.CONCLUSION:Secondary endoresection seems to be an effective treatment option for globe salvage in choroidal melanoma not responsive to conventional treatment and displaying persistent exudative retinal detachment.There was no visual acuity increase among the treated eyes but globe salvage was possible in most cases in this study.
文摘In a comprehensive literature review,PubMed,Embasem and Web of Science were searched for studies examining targeted therapy of ocular malignant melanomas to present and discuss targeted therapy treatment options of ocular tumors,mainly conjunctival and uveal melanoma(UM).Conjunctival malignant melanomas showed similarities in clinical and genetic aspects with cutaneous melanomas.Many therapies with checkpoint inhibitors already established for cutaneous melanomas may be a treatment option for conjunctival malignant melanomas with shared traits.Existing targeted therapies are for example checkpoint inhibitors like pembrolizumab or nivolumab.As a corollary,due to marked differences in clinics and genetics between UMs and conjunctival melanomas(CMs)or cutaneous melanomas,it has remained elusive whether the available possibilities of molecular targeted therapy will be an option for the therapy of metastasizing UMs.Possible novel ways of treating UM are being explored.Fotemustine or the inoculation of dendritic cells with tumorous RNA or sunitinib in combination with cisplatin and or tamoxifen may be used in future to treat UM.While CM are treatable using targeted therapies,UM have not been researched enough to find working targeted therapy options.Further research has to be done in order to find acceptable treatment options.
基金supported by National Natural Science Foundation of China(Grant Nos.81871990 and 31671448)Yunnan Applicative and Basic Research Program(Grant Nos.2019FY003030 and 202101AV070002)a grant(2019KF006)from Conservation and Utilization of Bio-Resources in Yunnan(YNCUB).
文摘Objective:The BRAF inhibitor,vemurafenib,has been widely used in the treatment of patients with melanoma-bearing BRAFV600E mutations.While the initial response to vemurafenib is usually excellent,the majority of patients eventually develop resistance and metastatic disease.However,the underlying molecular mechanism remains elusive.The objective of this study was therefore to identify additional molecular targets responsible for vemurafenib resistance.Methods:Western blots and immunohistochemistry analyses were used to evaluate expressions of PYK2 and p-PYK2 in cultured cells and melanoma tissue microarrays.The relationships of p-PYK2 with clinicopathological parameters were statistically analyzed.Invadopodia cell invasion,and a Ca2+assay were used to determine the effect of vemurafenib resistance-induced p-PYK2 on melanoma progression.A mouse model was used to assess the effects of PYK2 on melanoma metastasis.Results:Elevated p-PYK2 levels were detected in vemurafenib-resistant melanoma cells,and PYK2 was shown to regulate invadopodia formation in melanoma cells.Vemurafenib triggered invadopodia formation by activation of PYK2.Inhibition of PYK2 with either shRNA or the small molecule inhibitor,PF562711,dramatically reduced vemurafenib-induced invadopodia formation.Furthermore,knockdown of PYK2 significantly reduced melanoma lung metastasis in vivo.Increased expressions of p-PYK2 in melanoma patients were positively correlated with advanced stage(P=0.002),metastasis(P<0.001),and Clark grade(P<0.001),and were also associated with short overall survival[hazard ratio(HR)=3.304,P=0.007]and progression-free survival(HR=2.930,P=0.001).Conclusions:PYK2 mediated vemurafenib-induced melanoma cell migration and invasion.Inhibition of PYK2 resensitized melanoma cells to vemurafenib.Phospho-PYK2 was a prognostic biomarker in melanoma patients.
文摘Background: The anorectal location of melanomas is extremely rare (1% - 3% of all melanomas), and the prognosis remains poor because of the aggressiveness and the high metastatic potential of those tumors. The discovery that the KIT oncogene may be aberrantly activated in a subset of patients with anorectal melanoma creates a realm of possibility for the development of targeted molecular therapy. Aim: to show the epidemiologic, clinico-radiological, histological features and treatment management especially in patients with over-expression of C-KIT treated by Imatinib. Methods: It is a retrospective study conducted in the department of medical oncology at Hassan II University Hospital between January 2007 and January 2012, including all patients with histologically proven melanoma of the anorectal area. Results: 11 cases were collected, with slight female predominance. Nine patients were metastatic at the moment of diagnosis, and only two with local stage, but evolution was marked by local and distant recurrence less than 12 months after abdo-minoperineal resection. First line of chemotherapy was based mainly on paclitaxel, carboplatine and dacarbazine. Response was modest with only 3 partial responses, 4 patients with disease stability, and 4 patients with disease progression. Two patients, with over expression of C-KIT, received Imatinib as second line of treatment with significant improvement of symptoms and radiological response reaching 50%. Seven patients died with a median survival of 11 months from diagnosis to the date of death. Conclusion: Primary anorectal melanomas are very rare, with high aggressiveness and poor prognosis. Treatment management is still a big challenge given to the modest efficacy of conventional chemotherapy. Better understanding of carcinogenesis and signaling pathways will allow development of new targeted therapies.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
基金Supported by the National Natural Science Foundation of China(No.82460215)National Natural Science Foundation of China Pre-experimental Project(No.2025GZRYSY006)+4 种基金2025 Youth Training Project of the Xi’an Municipal Health Commission(No.2025qn05)Xi’an Medical Research-Discipline Capacity Building Project(No.23YXYJ0002)Key R&D Plan of Shaanxi Province:Key Industrial Innovation Chain(Cluster)-Social Development Field(No.2022ZDLSF03-10)Research Incubation Fund of Xi’an People’s Hospital(Xi’an Fourth HospitalNo.LH-13).
文摘AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.
基金supported through grants from the Key Fields of Biomedicine and Health Foundation of Colleges and Universities in Guangdong Province(2022ZDZX2017)the National Natural Science Foundation of China(82104354)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515012154)the funding grants from University of Macao and the University of Macao Development Foundation(MYRG2023-GRG00184-ICMS-UMDF and MYRG2024-GRG00271-ICMS-UMDF).
文摘The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constraints of conventional drug delivery methods by their superior safety and efficacy through precise targeting,while simultaneously enabling painless delivery.Currently,MNs are increasingly used as carriers for drug delivery,with the loading of insoluble drugs to improve their treatment efficiency or combining with bioactive substances for the construction of an efficient drug delivery system to maximize the effects of bioactive substances.The methods used for preparation MNs are diverse,enabling them to meet the requirements of most applications.The emergence of MNs has addressed the shortcomings associated with insoluble drugs,expanded the applications of bioactive substances,and improved their use in clinical practice.This review summarizes current information on the application of MNs in a variety of skin diseases,such as psoriasis,vitiligo,alopecia,hypertrophic scarring,atopic dermatitis,melanoma,acne,and skin infections.The current clinical applications and future opportunities for MNs in the treatment of skin diseases are also discussed.Despite substantial progress in the clinical application of MNs as delivery vectors,issues such as low drug loading and poor mechanical strength during MNs preparation remain the main challenges.Therefore,clinical implementation of MNs-based therapies remains limited,highlighting key opportunities for future research.
基金supported by grants from the Jagiellonian University,Poland(N18/DBS/000007)the Polish National Science Centre(2018/31/N/NZ4/03787).
文摘Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In solid tumors,angiogenesis supports growth,nutrient delivery,waste removal,and metastasis.Tumors can induce angiogenesis through proangiogenic factors including VEGF,FGF-2,PDGF,angiopoietins,HGF,TNF,IL-6,SCF,tryptase,and chymase.This balance is disrupted in tumors,and extracellular vesicles(EVs)contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells(ECs).Malignant melanoma,a particular type of skin cancer,accounts for only 1%of skin cancer cases but more than 75%of deaths.Its incidence has risen significantly,with a 40%increase between 2012 and 2022,especially in fair-skinned populations.Advanced metastatic stages have a high mortality due to delayed diagnosis.This review examines the molecular basis of angiogenesis in melanoma,focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.
文摘Objective:To evaluate the predictive value of the neutrophil⁃to⁃lymphocyte ratio(NLR)and the systemic immune⁃inflammation index(SII)in predicting patients with anti⁃melanoma differentiation⁃associated gene 5⁃positive(anti⁃MDA5+)dermatomyositis(DM)develop into the rapidly progressive interstitial lung disease(RPILD).Methods:We retrospectively analyzed the clinical and laboratory data of 124 anti⁃MDA5+DM patients from the First Affiliated Hospital of Nanjing Medical University between March 2019 and September 2023.We identified independent risk factors associated with the development and mortality of RPILD with the Cox regression analysis,and determined the optimal cut⁃off values for predicting adverse outcomes with the receiver operating characteristic(ROC)curve analysis.Results:Among the 124 patients,36 patients(29.03%)developed RPILD,and 39 patients(31.45%)died during the follow⁃up period.The results of multivariate Cox regression analysis showed that the elevated NLR was an independent risk factor for RPILD development,while the elevated SII expression was independently associated with the increased mortality of RPILD.Based on the ROC curve analysis,NLR>6.12 was a predictor for RPILD,and SII>875.79 was associated with increased mortality risk of RPILD.Conclusion:Both NLR and SII are accessible,cost⁃effective,and reliable prognostic indicators for the prognosis of patients with anti⁃MDA5^(+)DM,providing a valuable guidance for clinical management and risk stratification of the disease.
基金supported by the Russian Science Foundation,project no.23-14-00285。
文摘Melanomas are aggressive cancers,with a high rate of metastatic disease.Cutaneous(CM)and uveal(UM)melanomas are intrinsically different diseases,and most cell death inducers effective for CM do not function for UM.This is primarily due to the fact the eye is an immunologically privileged organ,and it fails to achieve the efficacy of immune checkpoint inhibitors(ICIs)comparable to that for CM.However,approaches utilizing specific melanomaassociated antigens are being developed for metastatic forms of CM and UM.The most promising to date are gp100 and tyrosinase related protein 1(TYRP1),primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor.The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis.Therefore,the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death.Here we consistently discuss the latest advances in the therapy of melanomas,and above all-UM,which is classified as an orphan disease.
基金supported by the Natural Science Foundation of Hebei Province(Grant number:C2025405060).
文摘Skin cutaneous melanoma(SKCM),a highly invasive malignant tumor originating from skin melanocytes,poses a significant threat to public health[1,2].Its development is closely associated with multiple factors,such as ultraviolet radiation,gene mutations,and immune escape.Among these,imbalance in the immune surveillance and clearance of tumor cells is a crucial link to disease progression[3,4].Tripartite motif-containing 27,which belongs to the TRIM protein family and is encoded by the TRIM27 gene,contains the RING,B-box,and coiled-coil domains.It participates in biological processes such as cell-cycle regulation,signal transduction,and immune response mainly by modifying target proteins through ubiquitination.Notably,increasing evidence indicates that TRIM27 is closely associated with the tumor immune microenvironment and contributes to cancer immune escape via multiple mechanisms,thereby promoting tumor development[5].However,the role of TRIM27 in SKCM remains unclear,thus prompting our investigation to elucidate this.
基金supported by the National Key Research and Development Project(No.2023YFC3404400)。
文摘Objective:Acral melanoma(AM),a unique subtype prevalent in China,develops on the palms,soles,and nail beds.Despite its distinct clinical and pathological features compared to cutaneous melanoma(CM),the molecular basis underlying these differences remains poorly understood.This study aims to perform a comprehensive comparative transcriptomic analysis of AM and CM at the single-cell level to uncover key molecular distinctions.Methods:We analyzed single-cell RNA sequencing(scRNA-seq)data from 39 AM patients and 18 CM cases.Single-cell transcriptomic profiling was used to compare tumor cell subpopulations and microenvironmental differences.Bioinformatics tools were employed for cell clustering,differential gene expression analysis,cell-cell communication network inferences,and survival analysis.Results:AM exhibited a significantly higher proportion of MPZ^(+)melanoma cells,a subpopulation with Schwann cell-like properties associated with poor prognosis.These MPZ^(+)melanoma cells established extensive communication networks with AM-specific immune and stromal components,prompting an immunosuppressive microenvironment and enhancing angiogenic potential.Survival analysis further indicated that the presence of MPZ^(+)melanoma cells is closely linked to worse clinical outcomes in AM patients.Conclusions:This study provides novel insights into the molecular distinctions between AM and CM,highlighting the critical role of MPZ^(+)melanoma cells in AM progression.These findings enhance our understanding of AM pathophysiology and may contribute to the development of more targeted therapeutic strategies.
文摘BACKGROUND Cutaneous melanoma is an aggressive skin cancer with high metastatic potential.Accurate staging is critical to guide therapeutic strategies and improve prognosis.Whole-body magnetic resonance imaging(WB-MRI),particularly when combined with diffusion-weighted imaging(DWI),has emerged as promising tool for comprehensive,radiation-free assessment of metastatic spread.AIM To systematically review the diagnostic performance and clinical utility of WBMRI in the staging and restaging of cutaneous melanoma,with comparison to conventional imaging modalities such as computed tomography(CT)and positron emission tomography/CT(PET/CT).METHODS A systematic literature review was conducted using PubMed,Embase,Scopus and Web of Science databases for studies published in the last 10 years.Inclusion criteria focused on comparative diagnostic accuracy studies of WB-MRI vs CT and PET/CT for melanoma staging.The methodological quality of the studies was appraised using the QUADAS-2 tool.RESULTS Sixteen studies involving over 700 patients met the inclusion criteria.WB-MRI showed high sensitivity(73%-90%)and specificity(up to 98%)in detecting metastases,particularly in bone,liver and soft tissue.DWI enhanced lesion detection,and WB-MRI often influenced clinical management decisions.However,CT outperformed WB-MRI in identifying small pulmonary nodules.AI-assisted analysis and contrastenhanced sequences further improved diagnostic confidence.CONCLUSION WB-MRI represents a robust imaging modality for staging cutaneous melanoma,offering superior soft-tissue contrast and functional imaging without ionizing radiation.Its strengths lie in detecting bone,liver and brain metastases.Challenges include limited lung lesion detection,cost,and availability.Advances in artificial intelligence,Hybrid PET/MRY systems,and radiomics are poised to expand WB-MRI’s role in personalized melanoma management.
文摘Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.
