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
Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic mel...Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.展开更多
AIM:To present the multi-omics landscape of cutaneous melanoma(CM)and uveal melanoma(UM)from The Cancer Genome Atlas(TCGA).METHODS:The differentially expressed genes(DEGs)between CM and UM were found and integrated in...AIM:To present the multi-omics landscape of cutaneous melanoma(CM)and uveal melanoma(UM)from The Cancer Genome Atlas(TCGA).METHODS:The differentially expressed genes(DEGs)between CM and UM were found and integrated into a gene ontology enrichment analysis.Besides,the differentially expressed miRNAs were also identified.We also compared the methylation level of CM with UM and identified the differentially methylated regions to integrate with the DEGs to display the relationship between the gene expression and DNA methylation.The differentially expressed transcription factors(TFs)were identified.RESULTS:Though CM had more mutational burden than UM,they shared several similarities such as the same rankings in diverse variant types.Except GNAQ and GNA11,the other top 18 mutated genes of the combined group were mostly detected in CM instead of UM.On the transcriptomic level,4610 DEGs were found and integrated into a gene ontology enrichment analysis.We also identified 485 differentially expressed miRNAs.The methylation analysis showed that UM had a significantly higher methylation level than CM.The integration of differentially methylated regions and DEGs demonstrated that most DEGs were downregulated in UM and the hypo-and hypermethylation presented no obvious difference within these DEGs.Finally,116 hypermethylated TFs and 114 hypomethylated TFs were identified as differentially expressed TFs in CM when compared with UM.CONCLUSION:This multi-omics study on comparing CM with UM confirms that they differ in all analyzed levels.Of notice,the results also offer new insights with implications for elucidating certain unclear problems such as the distinct role of epithelial mesenchymal transition in two melanomas,the different metastatic routes of CM and UM and the liver tropism of metastatic UM.展开更多
The incidence of cutaneous melanoma appears to be increasing worldwide and this is attributed to solar radiation exposure.Early diagnosis is a challenging task.Any clinically suspected lesion must be assessed by compl...The incidence of cutaneous melanoma appears to be increasing worldwide and this is attributed to solar radiation exposure.Early diagnosis is a challenging task.Any clinically suspected lesion must be assessed by complete diagnostic excision biopsy(margins 1-2 mm);however,there are other biopsy techniques that are less commonly used.Melanomas are characterized by Breslow thickness as thin(<1 mm),intermediate(1-4 mm)and thick(>4 mm).This thickness determines their biological behavior,therapy,prognosis and survival.If the biopsy is positive,a wide local excision(margins 1-2 cm)is finally performed.However,metastasis to regional lymph nodes is the most accurate prognostic determinant.Therefore,sentinel lymph node biopsy(SLNB)for diagnosed melanoma plays a pivotal role in the management strategy.Complete lymph node clearance has undoubted advantages and is recommended in all cases of positive SLN biopsy.A PET-CT(positron emission tomography-computed tomography)scan is necessary for staging and follow-up after treatment.Novel targeted therapies and immunotherapies have shown improved outcomes in advanced cases.展开更多
Human leukocyte antigen G (HLA-G) is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma (CMM), a series of 47 skin melanocytic lesions were...Human leukocyte antigen G (HLA-G) is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma (CMM), a series of 47 skin melanocytic lesions were immunohistochemically evaluated. The correlation between HLA-G expression and CMM clinicohistopahtological data and Bcl-2 expression was also analyzed. HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expression was significantly correlated with the inflammatory infiltration and Bcl-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathological subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvironment rather than a malignant feature of CMM.展开更多
Melanoma,characterized by high mortality,rapid development and accompanied with angio-genesis is the most typical malignant tumor in skin cancer.Hence,the detection of blood vessels is of much significanoe.The early v...Melanoma,characterized by high mortality,rapid development and accompanied with angio-genesis is the most typical malignant tumor in skin cancer.Hence,the detection of blood vessels is of much significanoe.The early vascular network has small scale.If we remove the tumor early and biopsy it,it will increase the spread of the cancer cells and infection and bleeding.In this case,we presented a new angiography method.A high-resolution OCT system for noninvasive an-giographic imaging of early skin melanoma-Swept Source Optical Coberence Tomography Angiography(SS-OCTA)is proposed.With a high lateral resolution of 10pm in vrivo tomographic angiography,SS-OCTA is used to image and identify the morphology of the early tumor blood vessels.In addition,a control group experiment is conducted to observe the growth of melanoma in the process of rupture,malormation of micro-vessels.The results of the analysis and statistical test(P<0.05)are statistically signifcant.展开更多
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
BACKGROUND Delays in sentinel lymph node(SLN)biopsy may affect the positivity of non-SLNs.For these reasons,effort is being directed at obtaining reliable information regarding SLN positivity prior to surgical excisio...BACKGROUND Delays in sentinel lymph node(SLN)biopsy may affect the positivity of non-SLNs.For these reasons,effort is being directed at obtaining reliable information regarding SLN positivity prior to surgical excision.However,the existing tools,e.g.,dermoscopy,do not recognize statistically significant predictive criteria for SLN positivity in melanomas.AIM To investigate the possible association of computer-assisted objectively obtained color,color texture,sharpness and geometry variables with SLN positivity.METHODS We retrospectively reviewed and analyzed the computerized medical records of all patients diagnosed with cutaneous melanoma in a tertiary hospital in Germany during a 3-year period.The study included patients with histologically confirmed melanomas with Breslow>0.75 mm who underwent lesion excision and SLN biopsy during the study period and who had clinical images shot with a digital camera and a handheld ruler aligned beside the lesion.RESULTS Ninety-nine patients with an equal number of lesions met the inclusion criteria and were included in the analysis.Overall mean(±standard deviation)age was 66(15)years.The study group consisted of 20 patients with tumor-positive SLN(SLN+)biopsy,who were compared to 79 patients with tumor-negative SLN biopsy specimen(control group).The two groups differed significantly in terms of age(61 years vs 68 years)and histological subtype,with the SLN+patients being younger and presenting more often with nodular or secondary nodular tumors(P<0.05).The study group patients showed significantly higher eccentricity(i.e.distance between color and geometrical midpoint)as well as higher sharpness(i.e.these lesions were more discrete from the surrounding normal skin,P<0.05).Regarding color variables,SLN+patients demonstrated higher range in all four color intensities(gray,red,green,blue)and significantly higher skewness in three color intensities(gray,red,blue),P<0.05.Color texture variables,i.e.lacunarity,were comparable in both groups.CONCLUSION SLN+patients demonstrated significantly higher eccentricity,higher sharpness,higher range in all four color intensities(gray,red,green,blue)and significantly higher skewness in three color intensities(gray,red,blue).Further prospective studies are needed to better understand the effectiveness of clinical image processing in SLN+melanoma patients.展开更多
The small bowel represents one of the main sites for cutaneous melanoma metastasis;however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year...The small bowel represents one of the main sites for cutaneous melanoma metastasis;however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.展开更多
Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by ...Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.展开更多
SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Ta...SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.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
BACKGROUND Primary intraspinal malignant melanoma is a very rare tumor that most often occurs in the cervical,thoracic,or thoracolumbar segment.CASE SUMMARY A rare case of primary thoracolumbar malignant melanoma is d...BACKGROUND Primary intraspinal malignant melanoma is a very rare tumor that most often occurs in the cervical,thoracic,or thoracolumbar segment.CASE SUMMARY A rare case of primary thoracolumbar malignant melanoma is described.A 45-year-old female patient complained of low back pain with numbness and fatigue in both lower limbs.MR revealed an intradural space-occupying lesion at the thoracic 12 to lumbar 1 level.The tumor was partially excised,and a malignant melanoma was confirmed by histopathology.CONCLUSION Primary intraspinal malignant melanoma has rarely been reported,and surgical resection and related characteristics and diagnoses have been discussed.展开更多
BACKGROUND Rectal mucosal melanoma is a rare and highly aggressive disease.Common symptoms include anal pain,an anal mass,or bleeding.As such,the disease is usually detected on rectal examination of patients with othe...BACKGROUND Rectal mucosal melanoma is a rare and highly aggressive disease.Common symptoms include anal pain,an anal mass,or bleeding.As such,the disease is usually detected on rectal examination of patients with other suspected anorectal diseases.However,due to its rarity and nonspecific symptoms,melanoma of the rectal mucosa is easily misdiagnosed.CASE SUMMARY This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months,without any identifiable cause.During colonoscopy,a bulge of approximately 2.2 cm×2.0 cm was identified.Subsequently,the patient underwent endoscopic ultrasound(EUS)to characterize the depth of invasion of the lesions.EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes.Following surgical intervention,the excised tissue samples were examined and confirmed to be rectal malignant melanoma.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.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
Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular ...Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.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
Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses w...Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.展开更多
Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis,...Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis, and management of various forms of cutaneous endometriosis. Material and Methods: It was an observational, retrospective and descriptive review of cases presenting with cutaneous endometriosis among Cameroonian women managed at the gynaecological outpatient department of Yaounde Gynaeco-Obstetric and Pediatric Hospital. All the following parameters were analysed: age, parity, previous pelvic surgery, presenting symptoms and duration, associated symptoms, localizations, imaging, size of the lesion, other localization of endometriosis, management and histopathological results. Results: we reported 4 cases of cutaneous endometriosis, with 3 umbilical endometriosis and 1 abdominal scar endometriosis. Patient age ranged from 28 to 39 years with an average of 33 years. All patients described infertility (two primary and two secondary) and two had a history of abdominal surgery. All patients presented local cyclical signs such as pain, swelling, color change and bleeding. The duration of symptoms varied from 2 to 3 years and the size of lesions ranged from 2 to 3.5 cm for umbilical lesions and was 9 cm for abdominal scar endometriosis. In all cases, no imaging was required for the diagnosis, which was suspected on the basis of patient’s history and the cyclical nature of local signs, followed by wide surgical excision and confirmation on histopathology. Conclusion: Cutaneaous endometriosis is a rare benign condition. Umbilical endometriosis seems to be the main cutaneous localization and can be described as primary or secondary. Even if its diagnosis must be confirmed by histopathology, it should be considered in patient with cutaneous cyclic signs such as pain, swelling or bleeding with or without history of abdominal surgery.展开更多
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.
文摘Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.
基金Supported by the China Scholarship Council(CSC)Program(No.201708080023,No.201708080104)Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of University of Tübingen。
文摘AIM:To present the multi-omics landscape of cutaneous melanoma(CM)and uveal melanoma(UM)from The Cancer Genome Atlas(TCGA).METHODS:The differentially expressed genes(DEGs)between CM and UM were found and integrated into a gene ontology enrichment analysis.Besides,the differentially expressed miRNAs were also identified.We also compared the methylation level of CM with UM and identified the differentially methylated regions to integrate with the DEGs to display the relationship between the gene expression and DNA methylation.The differentially expressed transcription factors(TFs)were identified.RESULTS:Though CM had more mutational burden than UM,they shared several similarities such as the same rankings in diverse variant types.Except GNAQ and GNA11,the other top 18 mutated genes of the combined group were mostly detected in CM instead of UM.On the transcriptomic level,4610 DEGs were found and integrated into a gene ontology enrichment analysis.We also identified 485 differentially expressed miRNAs.The methylation analysis showed that UM had a significantly higher methylation level than CM.The integration of differentially methylated regions and DEGs demonstrated that most DEGs were downregulated in UM and the hypo-and hypermethylation presented no obvious difference within these DEGs.Finally,116 hypermethylated TFs and 114 hypomethylated TFs were identified as differentially expressed TFs in CM when compared with UM.CONCLUSION:This multi-omics study on comparing CM with UM confirms that they differ in all analyzed levels.Of notice,the results also offer new insights with implications for elucidating certain unclear problems such as the distinct role of epithelial mesenchymal transition in two melanomas,the different metastatic routes of CM and UM and the liver tropism of metastatic UM.
文摘The incidence of cutaneous melanoma appears to be increasing worldwide and this is attributed to solar radiation exposure.Early diagnosis is a challenging task.Any clinically suspected lesion must be assessed by complete diagnostic excision biopsy(margins 1-2 mm);however,there are other biopsy techniques that are less commonly used.Melanomas are characterized by Breslow thickness as thin(<1 mm),intermediate(1-4 mm)and thick(>4 mm).This thickness determines their biological behavior,therapy,prognosis and survival.If the biopsy is positive,a wide local excision(margins 1-2 cm)is finally performed.However,metastasis to regional lymph nodes is the most accurate prognostic determinant.Therefore,sentinel lymph node biopsy(SLNB)for diagnosed melanoma plays a pivotal role in the management strategy.Complete lymph node clearance has undoubted advantages and is recommended in all cases of positive SLN biopsy.A PET-CT(positron emission tomography-computed tomography)scan is necessary for staging and follow-up after treatment.Novel targeted therapies and immunotherapies have shown improved outcomes in advanced cases.
文摘Human leukocyte antigen G (HLA-G) is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma (CMM), a series of 47 skin melanocytic lesions were immunohistochemically evaluated. The correlation between HLA-G expression and CMM clinicohistopahtological data and Bcl-2 expression was also analyzed. HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expression was significantly correlated with the inflammatory infiltration and Bcl-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathological subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvironment rather than a malignant feature of CMM.
基金supported by the Jiangsu Province Science Fund for Distinguished Young Scholars(BK20060010)the Frontier Science Research project of the Chinese Academy of Sciences(QYZDBS-SWJSC03)+2 种基金the National Natural Science Foundation of China(61675226)the National Key R&D Program of China(2017YFC0108200,2017YFB0403700)the Jiangsu Province Key R&D Program(BE2018667).
文摘Melanoma,characterized by high mortality,rapid development and accompanied with angio-genesis is the most typical malignant tumor in skin cancer.Hence,the detection of blood vessels is of much significanoe.The early vascular network has small scale.If we remove the tumor early and biopsy it,it will increase the spread of the cancer cells and infection and bleeding.In this case,we presented a new angiography method.A high-resolution OCT system for noninvasive an-giographic imaging of early skin melanoma-Swept Source Optical Coberence Tomography Angiography(SS-OCTA)is proposed.With a high lateral resolution of 10pm in vrivo tomographic angiography,SS-OCTA is used to image and identify the morphology of the early tumor blood vessels.In addition,a control group experiment is conducted to observe the growth of melanoma in the process of rupture,malormation of micro-vessels.The results of the analysis and statistical test(P<0.05)are statistically signifcant.
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.
文摘BACKGROUND Delays in sentinel lymph node(SLN)biopsy may affect the positivity of non-SLNs.For these reasons,effort is being directed at obtaining reliable information regarding SLN positivity prior to surgical excision.However,the existing tools,e.g.,dermoscopy,do not recognize statistically significant predictive criteria for SLN positivity in melanomas.AIM To investigate the possible association of computer-assisted objectively obtained color,color texture,sharpness and geometry variables with SLN positivity.METHODS We retrospectively reviewed and analyzed the computerized medical records of all patients diagnosed with cutaneous melanoma in a tertiary hospital in Germany during a 3-year period.The study included patients with histologically confirmed melanomas with Breslow>0.75 mm who underwent lesion excision and SLN biopsy during the study period and who had clinical images shot with a digital camera and a handheld ruler aligned beside the lesion.RESULTS Ninety-nine patients with an equal number of lesions met the inclusion criteria and were included in the analysis.Overall mean(±standard deviation)age was 66(15)years.The study group consisted of 20 patients with tumor-positive SLN(SLN+)biopsy,who were compared to 79 patients with tumor-negative SLN biopsy specimen(control group).The two groups differed significantly in terms of age(61 years vs 68 years)and histological subtype,with the SLN+patients being younger and presenting more often with nodular or secondary nodular tumors(P<0.05).The study group patients showed significantly higher eccentricity(i.e.distance between color and geometrical midpoint)as well as higher sharpness(i.e.these lesions were more discrete from the surrounding normal skin,P<0.05).Regarding color variables,SLN+patients demonstrated higher range in all four color intensities(gray,red,green,blue)and significantly higher skewness in three color intensities(gray,red,blue),P<0.05.Color texture variables,i.e.lacunarity,were comparable in both groups.CONCLUSION SLN+patients demonstrated significantly higher eccentricity,higher sharpness,higher range in all four color intensities(gray,red,green,blue)and significantly higher skewness in three color intensities(gray,red,blue).Further prospective studies are needed to better understand the effectiveness of clinical image processing in SLN+melanoma patients.
文摘The small bowel represents one of the main sites for cutaneous melanoma metastasis;however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.
文摘Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.
基金supported in part by the National Institutes of Health under award number K08CA255933.
文摘SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.
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.
文摘BACKGROUND Primary intraspinal malignant melanoma is a very rare tumor that most often occurs in the cervical,thoracic,or thoracolumbar segment.CASE SUMMARY A rare case of primary thoracolumbar malignant melanoma is described.A 45-year-old female patient complained of low back pain with numbness and fatigue in both lower limbs.MR revealed an intradural space-occupying lesion at the thoracic 12 to lumbar 1 level.The tumor was partially excised,and a malignant melanoma was confirmed by histopathology.CONCLUSION Primary intraspinal malignant melanoma has rarely been reported,and surgical resection and related characteristics and diagnoses have been discussed.
基金Supported by The Research Foundation of Wuhan Municipal Health Commission,No.WX21D02.
文摘BACKGROUND Rectal mucosal melanoma is a rare and highly aggressive disease.Common symptoms include anal pain,an anal mass,or bleeding.As such,the disease is usually detected on rectal examination of patients with other suspected anorectal diseases.However,due to its rarity and nonspecific symptoms,melanoma of the rectal mucosa is easily misdiagnosed.CASE SUMMARY This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months,without any identifiable cause.During colonoscopy,a bulge of approximately 2.2 cm×2.0 cm was identified.Subsequently,the patient underwent endoscopic ultrasound(EUS)to characterize the depth of invasion of the lesions.EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes.Following surgical intervention,the excised tissue samples were examined and confirmed to be rectal malignant melanoma.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.
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.
基金supported by the National Natural Science Foundation of China(Nos.82273159 and 82171838)the Jiangsu Province’s Science and Technology Project(No.BE2020722).
文摘Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.
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Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.
文摘Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis, and management of various forms of cutaneous endometriosis. Material and Methods: It was an observational, retrospective and descriptive review of cases presenting with cutaneous endometriosis among Cameroonian women managed at the gynaecological outpatient department of Yaounde Gynaeco-Obstetric and Pediatric Hospital. All the following parameters were analysed: age, parity, previous pelvic surgery, presenting symptoms and duration, associated symptoms, localizations, imaging, size of the lesion, other localization of endometriosis, management and histopathological results. Results: we reported 4 cases of cutaneous endometriosis, with 3 umbilical endometriosis and 1 abdominal scar endometriosis. Patient age ranged from 28 to 39 years with an average of 33 years. All patients described infertility (two primary and two secondary) and two had a history of abdominal surgery. All patients presented local cyclical signs such as pain, swelling, color change and bleeding. The duration of symptoms varied from 2 to 3 years and the size of lesions ranged from 2 to 3.5 cm for umbilical lesions and was 9 cm for abdominal scar endometriosis. In all cases, no imaging was required for the diagnosis, which was suspected on the basis of patient’s history and the cyclical nature of local signs, followed by wide surgical excision and confirmation on histopathology. Conclusion: Cutaneaous endometriosis is a rare benign condition. Umbilical endometriosis seems to be the main cutaneous localization and can be described as primary or secondary. Even if its diagnosis must be confirmed by histopathology, it should be considered in patient with cutaneous cyclic signs such as pain, swelling or bleeding with or without history of abdominal surgery.