Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-He...Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.展开更多
Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is ...Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.展开更多
Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interfe...Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.展开更多
Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and ...Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.展开更多
Background:Melanoma is a deadly skin tumor resulting from the malignant transformation of melanocytes.It is highly malignant and invasive,with the highest mortality rate among skin cancers.Acalypha australis L.(AAL),a...Background:Melanoma is a deadly skin tumor resulting from the malignant transformation of melanocytes.It is highly malignant and invasive,with the highest mortality rate among skin cancers.Acalypha australis L.(AAL),a plant with dual medicinal and culinary purposes,is commonly regarded as an edible wild vegetable in southern China.Additionally,AAL has a long history of medicinal use in China,often employed for its hemostatic,anti-diarrheal,and anti-inflammatory properties.Modern pharmacology has demonstrated that AAL possesses functions such as weight loss,antimicrobial activity,antiviral effects,and treatment for ulcerative colitis.However,there is currently no research available regarding its effectiveness and mechanisms of action on melanoma.Methods:In this investigation,we used methyl thiazolyl tetrazolium assay to detect cell viability,transwell assay to detect cell migration and invasion ability,and Western blot assay to detect relevant signaling pathways.Results:The present study reveals that 2 mg/mL AAL effectively suppresses the metastasis of B16 cells,while simultaneously triggering the expression of key apoptosis-related proteins,including Bcl-2,Bax,and cleaved caspased 3.Subsequent investigations demonstrate that AAL exerts this inhibitory effect via the PI3K/AKT signal transduction pathway,as evidenced by the observed deficits in Ras,AKT,p-AKT,and PI3K expression levels.Conclusion:These findings indicated that AAL could be a valuable therapeutic option for reducing the metastatic potential of B16 melanoma cells.展开更多
BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a pot...BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.CASE SUMMARY We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with antiprogrammed death-ligand 1(PD-L1)immunotherapy(pembrolizumab).After failing multiple lines of treatment,the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy.Following FMT,the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease.Despite a subsequent recurrence in the small bowel that was resected,the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.CONCLUSION The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.展开更多
The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is the...The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.展开更多
Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding o...Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accelerator by enhancing nicotinamide adenine dinucleotide(NAD^(+))synthesis.Therapeutically,DOT1L inhibition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.展开更多
Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Mel...Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.展开更多
Melanoma is a skin disease with high mortality rate while earlydiagnoses of the disease can increase the survival chances of patients. Itis challenging to automatically diagnose melanoma from dermoscopic skinsamples. ...Melanoma is a skin disease with high mortality rate while earlydiagnoses of the disease can increase the survival chances of patients. Itis challenging to automatically diagnose melanoma from dermoscopic skinsamples. Computer-Aided Diagnostic (CAD) tool saves time and effort indiagnosing melanoma compared to existing medical approaches. In this background,there is a need exists to design an automated classification modelfor melanoma that can utilize deep and rich feature datasets of an imagefor disease classification. The current study develops an Intelligent ArithmeticOptimization with Ensemble Deep Transfer Learning Based MelanomaClassification (IAOEDTT-MC) model. The proposed IAOEDTT-MC modelfocuses on identification and classification of melanoma from dermoscopicimages. To accomplish this, IAOEDTT-MC model applies image preprocessingat the initial stage in which Gabor Filtering (GF) technique is utilized.In addition, U-Net segmentation approach is employed to segment the lesionregions in dermoscopic images. Besides, an ensemble of DL models includingResNet50 and ElasticNet models is applied in this study. Moreover, AOalgorithm with Gated Recurrent Unit (GRU) method is utilized for identificationand classification of melanoma. The proposed IAOEDTT-MC methodwas experimentally validated with the help of benchmark datasets and theproposed model attained maximum accuracy of 92.09% on ISIC 2017 dataset.展开更多
Melanoma remains a serious illness which is a common formof skin cancer.Since the earlier detection of melanoma reduces the mortality rate,it is essential to design reliable and automated disease diagnosis model using...Melanoma remains a serious illness which is a common formof skin cancer.Since the earlier detection of melanoma reduces the mortality rate,it is essential to design reliable and automated disease diagnosis model using dermoscopic images.The recent advances in deep learning(DL)models find useful to examine the medical image and make proper decisions.In this study,an automated deep learning based melanoma detection and classification(ADL-MDC)model is presented.The goal of the ADL-MDC technique is to examine the dermoscopic images to determine the existence of melanoma.The ADL-MDC technique performs contrast enhancement and data augmentation at the initial stage.Besides,the k-means clustering technique is applied for the image segmentation process.In addition,Adagrad optimizer based Capsule Network(CapsNet)model is derived for effective feature extraction process.Lastly,crow search optimization(CSO)algorithm with sparse autoencoder(SAE)model is utilized for the melanoma classification process.The exploitation of the Adagrad and CSO algorithm helps to properly accomplish improved performance.A wide range of simulation analyses is carried out on benchmark datasets and the results are inspected under several aspects.The simulation results reported the enhanced performance of the ADL-MDC technique over the recent approaches.展开更多
BACKGROUND Melanoma is the most aggressive form of skin cancer,with a tendency to metastasize to any organ.Malignant melanoma is the most frequent cause of skin cancer-related deaths worldwide.Small intestine cancers ...BACKGROUND Melanoma is the most aggressive form of skin cancer,with a tendency to metastasize to any organ.Malignant melanoma is the most frequent cause of skin cancer-related deaths worldwide.Small intestine cancers especially small intestine metastases are relatively rare.Small intestine metastases are seldom described and likely underdiagnosed.Intussusception is most common in pediatric age,and in adults are almost 5%of all cases.CASE SUMMARY A 75-year-old man with a history of acral malignant melanoma was admitted to the Gastroenterology Department of our hospital,complaining of intermittent melena for 1 mo.Magnetic resonance enterography showed partial thickening of the jejunal wall and formation of a soft tissue mass,indicating a neoplastic lesion with jejunojejunal intussusception.The patient underwent partial small bowel resection.Pathological findings and immunohistochemical staining indicated small intestine metastatic melanoma.The patient refused further anti-tumor treatment after the surgery.Ten months after the first surgery,the patient presented with melena again.Computed tomography enterography showed the anastomotic stoma was normal without thickening of the intestinal wall,and routine conservative treatment was given.Three months later,the patient developed melena again.The patient underwent a second surgery,and multiple metastatic melanoma lesions were found.The patient refused adjuvant anti-tumor treatment and was alive at the latest follow-up.CONCLUSION Small intestine metastatic melanoma should be suspected in any patient with a history of malignant melanoma and gastrointestinal symptoms.展开更多
Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of...Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.展开更多
Dear Editor,Uveal melanoma(UM)is the most common primary intraocular malignancy in adults[1].We are writing to present a case of recurrent UM.This case presents an important clinical challenge:vision preservation in p...Dear Editor,Uveal melanoma(UM)is the most common primary intraocular malignancy in adults[1].We are writing to present a case of recurrent UM.This case presents an important clinical challenge:vision preservation in patients with recurrent anterior UM,especially in young patients.Informed consent was obtained from the patient.This case study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Beijing Tongren Hospital(approval number:TRECKY2018-056).展开更多
Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM r...Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.展开更多
Chemotherapy remains an important approach for the treatment of liver metastases from uveal melanoma(UM).Compared with systemic chemotherapy,regional chemotherapy has similar efficacy and fewer systemic adverse effect...Chemotherapy remains an important approach for the treatment of liver metastases from uveal melanoma(UM).Compared with systemic chemotherapy,regional chemotherapy has similar efficacy and fewer systemic adverse effects.Regional chemotherapy for UM liver metastases includes hepatic ar ter y infusion(HAI),transarterial chemoembolization(TACE),and isolated hepatic perfusion(IHP).In this review,we aim to examine the efficacy of regional chemotherapy and compare HAI,TACE,and IHP in terms of overall survival(OS).The three approaches showed no obvious difference in OS results.展开更多
BACKGROUND Malignant melanoma(MM)has shown an increasing incidence worldwide,and a potential to metastasize to almost any part of the body.Clinically,MM with bone metastasis as the initial manifestation is extremely r...BACKGROUND Malignant melanoma(MM)has shown an increasing incidence worldwide,and a potential to metastasize to almost any part of the body.Clinically,MM with bone metastasis as the initial manifestation is extremely rare.Spinal metastatic MM can cause spinal cord or nerve root compression,resulting in severe pain and paralysis.Currently,the primary clinical treatments for MM are surgical resection in conjunction with chemotherapy,radiotherapy,and immunotherapy.CASE SUMMARY Here,we report the case of a 52-year-old male who presented to the clinic with progressive low back pain and limited nerve function.No primary lesion or spinal cord compression was detected from computed tomography and magnetic resonance imaging of the lumbar vertebrae and positron emission tomography scan.A lumbar puncture biopsy confirmed the diagnosis of lumbar spine metastatic MM.Following surgical resection,the patient’s quality of life improved,symptoms were relieved,and comprehensive treatment was initiated,which prevented recurrence.CONCLUSION Spinal metastatic MM is clinically rare,and may cause neurological symptoms,including paraplegia.Currently,the clinical treatment plan consists of surgical resection in combination with chemotherapy,radiotherapy,and immunotherapy.展开更多
BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE...BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.展开更多
Melanoma is a perfidious form of skin cancer.The study offers a hybrid framework for the automatic classification of melanoma.An Auto-matic Melanoma Detection System(AMDS)is used for identifying melanoma from the infe...Melanoma is a perfidious form of skin cancer.The study offers a hybrid framework for the automatic classification of melanoma.An Auto-matic Melanoma Detection System(AMDS)is used for identifying melanoma from the infected area of the skin image using image processing techniques.A larger number of pre-existing automatic melanoma detection systems are either commercial or their accuracy can be further improved.The research problem is to identify the best preprocessing technique,feature extractor,and classifier for melanoma detection using publically available MED-NODE data set.AMDS goes through four stages.The preprocessing stage is for noise removal;the segmentation stage is for extracting lesions from infected skin images;the feature extraction stage is for determining the features like asymmetry,border,and color,and the classification stage is to classify the lesion as benign or melanoma.The infected input image for the AMDS may contain impurities such as noise,illumination,artifacts,and hairs.In the proposed methodology an algorithm LePrePro is proposed for the prepro-cessing stage for denoising and brightness cum contrast normalization and another algorithm LeFET is proposed for extending the feature vector space in the feature extraction stage using a hybrid approach.In the study,a novel approach has been proposed in which different classifiers,feature extractions,and data preprocessing steps of the AMDS are compared.In a conclusion,this comparison revealed that on experimentation using Med-Node and ISIC 2017 Dataset,the best results included Gaussian blur as the best data preprocessing step,Extended feature vector which is the combination of Hue Saturation Value(HSV),and Local Binary Pattern(LBP)was the best feature extraction method,and the ensemble bagged tree was the best classification technique on the Med-Node data sets with 99%Area Under the Receiver Operating Characteristic Curve(AUC),93.52%accuracy,90.82%sensitivity,and 98.36%specificity in the proposed automatic melanoma detection system.展开更多
BACKGROUND Malignant melanoma of the prostate is rare.Twenty-five studies describing 45 cases have been reported.Prostate melanoma is characterized by an insidious onset and poor prognosis.The prognosis and treatment ...BACKGROUND Malignant melanoma of the prostate is rare.Twenty-five studies describing 45 cases have been reported.Prostate melanoma is characterized by an insidious onset and poor prognosis.The prognosis and treatment vary according to primary or secondary melanoma.CASE SUMMARY A 75-year-old man attended the hospital due to low back pain of 2 mo duration.He denied a history of trauma or abnormal urinary symptoms.Digital rectal examination showed indentation in the left lobe of the prostate,1 cm in diameter.His prostate-specific antigen was 5.6 ng/mL and 18F-fluorodeoxyglucose positron emission tomography computed tomography(18F-FDG-PET/CT)showed focal glucose metabolism in the left lobe.Imaging showed bone metastases to T12 and bilateral ribs.Transperineal prostate biopsy was done and three tissue specimens on the left side showed prostate adenocarcinoma(Gleason score 3+3=6),but the specimen on the right side showed malignant melanoma.The patient underwent T12 tumor resection and pathology findings indicated metastatic malignant melanoma.The patient underwent gastroscopy and colonoscopy,and gastroscopy revealed multiple mucosal black spots in the gastric body and fundus.The patient was diagnosed with secondary malignant prostate melanoma and primary gastric disease.CONCLUSION Diagnosis of primary prostate melanoma requires caution and 18F-FDG-PET/CT may result in false-negative detection of melanoma.展开更多
基金supported by the Priority Research Centers Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(Grant 2017R1A6A03015562 and RS-2023-00237386).
文摘Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.
基金supported by the Gusu Medical Key Talent Project of Suzhou City of China(GSWS2020005)the New Pharmaceutics and Medical Apparatuses Project of Suzhou City of China(SLJ2021007)+3 种基金the Suzhou City Key Clinical Disease Diagnosis and Treatment Technology Special Project,China(LCZX202129)Wujiang Science and Educational Health Revitalization Fund Project,Suzhou,China(WWK202015)the Scientific Research Project of Suzhou Ninth People’s Hospital,Suzhou,China(YK202008)and Suzhou“Science and Education”Youth Science and Technology Project,Suzhou,China(KJXW2020075).
文摘Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.
文摘Uveal melanoma(UM)is the most common primary intraocular cancer in adults.The incidence in Europe and the United States is 6-7 per million population per year.Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 year.To date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor prognosis.No standard therapeutic approaches for its prevention or treatment have been established.The application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular disease.This is due to UM’s distinct genetics,natural history,and complex interaction with the immune system.Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or GNA11.As a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being studied.In this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.
基金This work was supported by the Hunan Education Department Project(NO.20A390)National Innovation and Entrepreneurship Training Program(S202010548007).
文摘Background:Melanoma is a deadly skin tumor resulting from the malignant transformation of melanocytes.It is highly malignant and invasive,with the highest mortality rate among skin cancers.Acalypha australis L.(AAL),a plant with dual medicinal and culinary purposes,is commonly regarded as an edible wild vegetable in southern China.Additionally,AAL has a long history of medicinal use in China,often employed for its hemostatic,anti-diarrheal,and anti-inflammatory properties.Modern pharmacology has demonstrated that AAL possesses functions such as weight loss,antimicrobial activity,antiviral effects,and treatment for ulcerative colitis.However,there is currently no research available regarding its effectiveness and mechanisms of action on melanoma.Methods:In this investigation,we used methyl thiazolyl tetrazolium assay to detect cell viability,transwell assay to detect cell migration and invasion ability,and Western blot assay to detect relevant signaling pathways.Results:The present study reveals that 2 mg/mL AAL effectively suppresses the metastasis of B16 cells,while simultaneously triggering the expression of key apoptosis-related proteins,including Bcl-2,Bax,and cleaved caspased 3.Subsequent investigations demonstrate that AAL exerts this inhibitory effect via the PI3K/AKT signal transduction pathway,as evidenced by the observed deficits in Ras,AKT,p-AKT,and PI3K expression levels.Conclusion:These findings indicated that AAL could be a valuable therapeutic option for reducing the metastatic potential of B16 melanoma cells.
文摘BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.CASE SUMMARY We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with antiprogrammed death-ligand 1(PD-L1)immunotherapy(pembrolizumab).After failing multiple lines of treatment,the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy.Following FMT,the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease.Despite a subsequent recurrence in the small bowel that was resected,the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.CONCLUSION The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.
文摘The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.
基金supported by grants from Shanghai Key Clinical Specialty,Shanghai Eye Disease Research Center(Grant No.:2022Zz01003 to Xianqun Fan)the National Key Research and Development Plan(Grant No.:2018YFC1106100 to Xianqun Fan)+1 种基金the National Natural Science Foundation of China(Grant Nos.:12275178 to Shengfang Ge and 82103240 to Peiwei Chai)Innovative Research Team of High-level Local Universities in Shanghai(Grant Nos.:SHSMU-ZDCX20210902 to Renbing Jia and SHSMUZDCX20210900 to Xianqun Fan),the Science and Technology Commission of Shanghai(Grant No.:19JC1410200 to Xianqun Fan),and Cross-disciplinary Research Fund of Shanghai Ninth People's Hospital,Shanghai Jiao Tong university School of Medicine(Grant No.:JYJC202210 to Ai Zhuang).
文摘Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accelerator by enhancing nicotinamide adenine dinucleotide(NAD^(+))synthesis.Therapeutically,DOT1L inhibition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.
基金supported by the Top Talent Project of Jiangsu Provincial People’s Hospital(No.YNRCZN0310).
文摘Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.
基金supported by the MSIT (Ministry of Science and ICT),Korea,under the ICAN (ICT Challenge and Advanced Network of HRD)program (IITP-2022-2020-0-01832)supervised by the IITP (Institute of Information&Communications Technology Planning&Evaluation)and the Soonchunhyang University Research Fund.
文摘Melanoma is a skin disease with high mortality rate while earlydiagnoses of the disease can increase the survival chances of patients. Itis challenging to automatically diagnose melanoma from dermoscopic skinsamples. Computer-Aided Diagnostic (CAD) tool saves time and effort indiagnosing melanoma compared to existing medical approaches. In this background,there is a need exists to design an automated classification modelfor melanoma that can utilize deep and rich feature datasets of an imagefor disease classification. The current study develops an Intelligent ArithmeticOptimization with Ensemble Deep Transfer Learning Based MelanomaClassification (IAOEDTT-MC) model. The proposed IAOEDTT-MC modelfocuses on identification and classification of melanoma from dermoscopicimages. To accomplish this, IAOEDTT-MC model applies image preprocessingat the initial stage in which Gabor Filtering (GF) technique is utilized.In addition, U-Net segmentation approach is employed to segment the lesionregions in dermoscopic images. Besides, an ensemble of DL models includingResNet50 and ElasticNet models is applied in this study. Moreover, AOalgorithm with Gated Recurrent Unit (GRU) method is utilized for identificationand classification of melanoma. The proposed IAOEDTT-MC methodwas experimentally validated with the help of benchmark datasets and theproposed model attained maximum accuracy of 92.09% on ISIC 2017 dataset.
基金the Deanship of Scientific Research at King Khalid University for funding this work under Grant Number(RGP 1/80/43)Princess Nourah bint Abdulrahman University Researchers Supporting Project Number(PNURSP2022R191)Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Melanoma remains a serious illness which is a common formof skin cancer.Since the earlier detection of melanoma reduces the mortality rate,it is essential to design reliable and automated disease diagnosis model using dermoscopic images.The recent advances in deep learning(DL)models find useful to examine the medical image and make proper decisions.In this study,an automated deep learning based melanoma detection and classification(ADL-MDC)model is presented.The goal of the ADL-MDC technique is to examine the dermoscopic images to determine the existence of melanoma.The ADL-MDC technique performs contrast enhancement and data augmentation at the initial stage.Besides,the k-means clustering technique is applied for the image segmentation process.In addition,Adagrad optimizer based Capsule Network(CapsNet)model is derived for effective feature extraction process.Lastly,crow search optimization(CSO)algorithm with sparse autoencoder(SAE)model is utilized for the melanoma classification process.The exploitation of the Adagrad and CSO algorithm helps to properly accomplish improved performance.A wide range of simulation analyses is carried out on benchmark datasets and the results are inspected under several aspects.The simulation results reported the enhanced performance of the ADL-MDC technique over the recent approaches.
基金Supported by National Natural Science Foundation of China,No.82100568.
文摘BACKGROUND Melanoma is the most aggressive form of skin cancer,with a tendency to metastasize to any organ.Malignant melanoma is the most frequent cause of skin cancer-related deaths worldwide.Small intestine cancers especially small intestine metastases are relatively rare.Small intestine metastases are seldom described and likely underdiagnosed.Intussusception is most common in pediatric age,and in adults are almost 5%of all cases.CASE SUMMARY A 75-year-old man with a history of acral malignant melanoma was admitted to the Gastroenterology Department of our hospital,complaining of intermittent melena for 1 mo.Magnetic resonance enterography showed partial thickening of the jejunal wall and formation of a soft tissue mass,indicating a neoplastic lesion with jejunojejunal intussusception.The patient underwent partial small bowel resection.Pathological findings and immunohistochemical staining indicated small intestine metastatic melanoma.The patient refused further anti-tumor treatment after the surgery.Ten months after the first surgery,the patient presented with melena again.Computed tomography enterography showed the anastomotic stoma was normal without thickening of the intestinal wall,and routine conservative treatment was given.Three months later,the patient developed melena again.The patient underwent a second surgery,and multiple metastatic melanoma lesions were found.The patient refused adjuvant anti-tumor treatment and was alive at the latest follow-up.CONCLUSION Small intestine metastatic melanoma should be suspected in any patient with a history of malignant melanoma and gastrointestinal symptoms.
基金This work was supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2023R1A2C1006268 and RS-2023-00212560).
文摘Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.
基金Supported by National Natural Science Foundation of China(No.82141128)the Capital Health Research and Development of Special(No.2020-1-2052)+4 种基金Beijing Natural Science Foundation(No.7204245)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045,No.Z181100001818003)Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM202010025018)Beijing Municipal Administration of Hospitals’Youth Programme(No.QML20190202)Beijing Dongcheng District Outstanding Talents Cultivating Plan(No.2018).
文摘Dear Editor,Uveal melanoma(UM)is the most common primary intraocular malignancy in adults[1].We are writing to present a case of recurrent UM.This case presents an important clinical challenge:vision preservation in patients with recurrent anterior UM,especially in young patients.Informed consent was obtained from the patient.This case study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Beijing Tongren Hospital(approval number:TRECKY2018-056).
基金supported by the National Natural Science Foundation of China(Grant Number[No.82071956])and the Clinical Research Plan of Shanghai Hospital Development Center(Grant Number[No.2020CR4065]).
文摘Glutamine metabolism(GM)plays an important role in tumor growth and proliferation.Skin cutaneous melanoma(SKCM)is a glutamine-dependent cancer.However,the molecular characteristics and action mechanism of GM on SKCM remain unclear.Therefore,we aimed to explore the effects of GM-related genes on survival,clinicopathological characteristics,and the tumor microenvironment in SKCM.In this study,682 SKCM samples were obtained from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Consensus clustering was used to classify SKCM samples into distinct subtypes based on 41 GM-related genes.Differences in survival,immune infiltration,clinical characteristics,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways as well as differentially expressed genes(DEGs)between subgroups were evaluated.A prognostic model was constructed according to prognostic DEGs.Differential analyses in survival,immune infiltration,tumor microenvironment(TME),tumor mutation burden(TMB),stemness,and drug sensitivity between risk groups were conducted.We identified two distinct GM-related subtypes on SKCM and found that GM-related gene alterations were associated with survival probability,clinical features,biological function,and immune infiltration.Then a risk model based on six DEGs(IL18,SEMA6A,PAEP,TNFRSF17,AIM2,and CXCL10)was constructed and validated for predicting overall survival in SKCM patients.The results showed that the risk score was negatively correlated with CD8+T cells,activated CD4+memory T cells,M1 macrophages,andγδT cells.The group with a low-risk score was accompanied by a better survival rate with higher TME scores and lower stemness index.Moreover,the group with high-and low-risk score had a significant difference with the sensitivity of 75 drugs(p<0.001).Overall,distinct subtypes in SKCM patients based on GM-related genes were identified and the risk model was constructed,which might contribute to prognosis prediction,guide clinical therapy,and develop novel therapeutic strategies.
基金Supported by National Natural Science Foundation of China(No.82141128)The Capital Health Research and Development of Special(No.2020-1-2052)+4 种基金Beijing Natural Science Foundation(No.7204245)Science&Technology Project of Beijing Municipal Science&Technology Commission(No.Z201100005520045,No.Z181100001818003)Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM202010025018)Beijing Municipal Administration of Hospitals’Youth Programme(No.QML20190202)Beijing Dongcheng District Outstanding Talents Cultivating Plan(No.2018)。
文摘Chemotherapy remains an important approach for the treatment of liver metastases from uveal melanoma(UM).Compared with systemic chemotherapy,regional chemotherapy has similar efficacy and fewer systemic adverse effects.Regional chemotherapy for UM liver metastases includes hepatic ar ter y infusion(HAI),transarterial chemoembolization(TACE),and isolated hepatic perfusion(IHP).In this review,we aim to examine the efficacy of regional chemotherapy and compare HAI,TACE,and IHP in terms of overall survival(OS).The three approaches showed no obvious difference in OS results.
基金Supported by The National Defense Science and Technology Foundation Enhancement Plan,No.2019-JCJQ-JJ-147.
文摘BACKGROUND Malignant melanoma(MM)has shown an increasing incidence worldwide,and a potential to metastasize to almost any part of the body.Clinically,MM with bone metastasis as the initial manifestation is extremely rare.Spinal metastatic MM can cause spinal cord or nerve root compression,resulting in severe pain and paralysis.Currently,the primary clinical treatments for MM are surgical resection in conjunction with chemotherapy,radiotherapy,and immunotherapy.CASE SUMMARY Here,we report the case of a 52-year-old male who presented to the clinic with progressive low back pain and limited nerve function.No primary lesion or spinal cord compression was detected from computed tomography and magnetic resonance imaging of the lumbar vertebrae and positron emission tomography scan.A lumbar puncture biopsy confirmed the diagnosis of lumbar spine metastatic MM.Following surgical resection,the patient’s quality of life improved,symptoms were relieved,and comprehensive treatment was initiated,which prevented recurrence.CONCLUSION Spinal metastatic MM is clinically rare,and may cause neurological symptoms,including paraplegia.Currently,the clinical treatment plan consists of surgical resection in combination with chemotherapy,radiotherapy,and immunotherapy.
文摘BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.
文摘Melanoma is a perfidious form of skin cancer.The study offers a hybrid framework for the automatic classification of melanoma.An Auto-matic Melanoma Detection System(AMDS)is used for identifying melanoma from the infected area of the skin image using image processing techniques.A larger number of pre-existing automatic melanoma detection systems are either commercial or their accuracy can be further improved.The research problem is to identify the best preprocessing technique,feature extractor,and classifier for melanoma detection using publically available MED-NODE data set.AMDS goes through four stages.The preprocessing stage is for noise removal;the segmentation stage is for extracting lesions from infected skin images;the feature extraction stage is for determining the features like asymmetry,border,and color,and the classification stage is to classify the lesion as benign or melanoma.The infected input image for the AMDS may contain impurities such as noise,illumination,artifacts,and hairs.In the proposed methodology an algorithm LePrePro is proposed for the prepro-cessing stage for denoising and brightness cum contrast normalization and another algorithm LeFET is proposed for extending the feature vector space in the feature extraction stage using a hybrid approach.In the study,a novel approach has been proposed in which different classifiers,feature extractions,and data preprocessing steps of the AMDS are compared.In a conclusion,this comparison revealed that on experimentation using Med-Node and ISIC 2017 Dataset,the best results included Gaussian blur as the best data preprocessing step,Extended feature vector which is the combination of Hue Saturation Value(HSV),and Local Binary Pattern(LBP)was the best feature extraction method,and the ensemble bagged tree was the best classification technique on the Med-Node data sets with 99%Area Under the Receiver Operating Characteristic Curve(AUC),93.52%accuracy,90.82%sensitivity,and 98.36%specificity in the proposed automatic melanoma detection system.
文摘BACKGROUND Malignant melanoma of the prostate is rare.Twenty-five studies describing 45 cases have been reported.Prostate melanoma is characterized by an insidious onset and poor prognosis.The prognosis and treatment vary according to primary or secondary melanoma.CASE SUMMARY A 75-year-old man attended the hospital due to low back pain of 2 mo duration.He denied a history of trauma or abnormal urinary symptoms.Digital rectal examination showed indentation in the left lobe of the prostate,1 cm in diameter.His prostate-specific antigen was 5.6 ng/mL and 18F-fluorodeoxyglucose positron emission tomography computed tomography(18F-FDG-PET/CT)showed focal glucose metabolism in the left lobe.Imaging showed bone metastases to T12 and bilateral ribs.Transperineal prostate biopsy was done and three tissue specimens on the left side showed prostate adenocarcinoma(Gleason score 3+3=6),but the specimen on the right side showed malignant melanoma.The patient underwent T12 tumor resection and pathology findings indicated metastatic malignant melanoma.The patient underwent gastroscopy and colonoscopy,and gastroscopy revealed multiple mucosal black spots in the gastric body and fundus.The patient was diagnosed with secondary malignant prostate melanoma and primary gastric disease.CONCLUSION Diagnosis of primary prostate melanoma requires caution and 18F-FDG-PET/CT may result in false-negative detection of melanoma.
