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
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
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
The aim is to evaluate the profile of cutaneous melanoma in rural and urban areas of the State of Espírito Santo and compare the results between them.The information collected included gender and age at diagnosis...The aim is to evaluate the profile of cutaneous melanoma in rural and urban areas of the State of Espírito Santo and compare the results between them.The information collected included gender and age at diagnosis,city of residence,tumor morphology,anatomic site,histological subtype,level of invasion,tumor thickness and staging.A retrospective observational study was conducted,using the Pathology Department’s database of Hospital Universitário Cassiano Antonio de Moraes(HUCAM).Statistical analysis was performed using SPSS Statistics.A total of 258 histopathological reports of Cutaneous Melanomas were identified between 2003 and 2016.This skin cancer was more common among women,in the age group from 50 to 79 years.The majority of lesions was localized in the malar region of the face,usually classified as in situ or with superficial invasion and presented Breslow’s thickness less than 1 mm.Regarding the diagnosis,the male population was older and had more aggressive melanomas with higher rates of Clark’s levels IV and V and Breslow’s thickness when compared to the female group.There was a great concentration of patients in the central mesoregion(173 cases—67.06%),probably because this is the most populous regional area of Espírito Santo.The prevalence of melanoma between 2003-2016 was higher in the rural area(21.52 cases/100,000 habitants)when compared to the urban area(4.15 cases/100,000 habitants).展开更多
目的初步探讨TC2N基因对皮肤黑色素瘤(skin cutaneous melanoma,SKCM)发生的影响及其作用机制。方法使用人类蛋白质图谱(The Human Protein Atlas,HPA)和肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库分析TC2N在SKCM中的表达及与...目的初步探讨TC2N基因对皮肤黑色素瘤(skin cutaneous melanoma,SKCM)发生的影响及其作用机制。方法使用人类蛋白质图谱(The Human Protein Atlas,HPA)和肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库分析TC2N在SKCM中的表达及与临床病理特征的关系。利用人黑色素瘤A375构建TC2N基因的过表达细胞模型,采用CCK-8法检测TC2N在细胞增殖中的作用。利用TC2N基因敲除小鼠构建皮肤黑色素移植瘤模型,观察并测量移植瘤的生长,通过免疫组化测定Ki67在移植瘤组织中的表达,分析肿瘤细胞的增殖。此外,进行基因集富集分析(Gene Set Enrichment Analysis,GSEA)探索TC2N表达与ERK/MAPK信号通路的相关性,并利用RT-qPCR和Western blot法检测相关基因CyclinD1、c-Myc、CDK2和CyclinE1在体内外的mRNA及蛋白表达水平。结果与正常皮肤组织比较,SKCM组织中TC2N的表达水平更高,且TC2N基因的高表达与SKCM患者的临床病理分期和淋巴结转移显著相关(P<0.05)。体外细胞实验发现,过表达TC2N基因后,A375细胞的增殖能力显著增加(P<0.05)。敲除小鼠皮下移植瘤模型结果显示,与TC2N^(+/+)小鼠比较,TC2N-/-小鼠肿瘤质量和体积明显降低(P<0.05),提示TC2N基因敲除后显著抑制SKCM的生长。GSEA富集分析提示TC2N与MAPK信号通路显著相关(P<0.01),且TC2N基因与ERK/MAPK下游基因表达呈正相关(P<0.01)。体内外实验均发现,TC2N表达显著促进ERK与p-ERK表达,且影响ERK相关分子CyclinD1、c-Myc、CDK2和CyclinE1的mRNA和蛋白的表达水平(P<0.01)。结论TC2N基因可能通过激活ERK/MAPK信号通路促进皮肤黑色素瘤的生长。展开更多
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.
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.
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The aim is to evaluate the profile of cutaneous melanoma in rural and urban areas of the State of Espírito Santo and compare the results between them.The information collected included gender and age at diagnosis,city of residence,tumor morphology,anatomic site,histological subtype,level of invasion,tumor thickness and staging.A retrospective observational study was conducted,using the Pathology Department’s database of Hospital Universitário Cassiano Antonio de Moraes(HUCAM).Statistical analysis was performed using SPSS Statistics.A total of 258 histopathological reports of Cutaneous Melanomas were identified between 2003 and 2016.This skin cancer was more common among women,in the age group from 50 to 79 years.The majority of lesions was localized in the malar region of the face,usually classified as in situ or with superficial invasion and presented Breslow’s thickness less than 1 mm.Regarding the diagnosis,the male population was older and had more aggressive melanomas with higher rates of Clark’s levels IV and V and Breslow’s thickness when compared to the female group.There was a great concentration of patients in the central mesoregion(173 cases—67.06%),probably because this is the most populous regional area of Espírito Santo.The prevalence of melanoma between 2003-2016 was higher in the rural area(21.52 cases/100,000 habitants)when compared to the urban area(4.15 cases/100,000 habitants).
文摘目的初步探讨TC2N基因对皮肤黑色素瘤(skin cutaneous melanoma,SKCM)发生的影响及其作用机制。方法使用人类蛋白质图谱(The Human Protein Atlas,HPA)和肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库分析TC2N在SKCM中的表达及与临床病理特征的关系。利用人黑色素瘤A375构建TC2N基因的过表达细胞模型,采用CCK-8法检测TC2N在细胞增殖中的作用。利用TC2N基因敲除小鼠构建皮肤黑色素移植瘤模型,观察并测量移植瘤的生长,通过免疫组化测定Ki67在移植瘤组织中的表达,分析肿瘤细胞的增殖。此外,进行基因集富集分析(Gene Set Enrichment Analysis,GSEA)探索TC2N表达与ERK/MAPK信号通路的相关性,并利用RT-qPCR和Western blot法检测相关基因CyclinD1、c-Myc、CDK2和CyclinE1在体内外的mRNA及蛋白表达水平。结果与正常皮肤组织比较,SKCM组织中TC2N的表达水平更高,且TC2N基因的高表达与SKCM患者的临床病理分期和淋巴结转移显著相关(P<0.05)。体外细胞实验发现,过表达TC2N基因后,A375细胞的增殖能力显著增加(P<0.05)。敲除小鼠皮下移植瘤模型结果显示,与TC2N^(+/+)小鼠比较,TC2N-/-小鼠肿瘤质量和体积明显降低(P<0.05),提示TC2N基因敲除后显著抑制SKCM的生长。GSEA富集分析提示TC2N与MAPK信号通路显著相关(P<0.01),且TC2N基因与ERK/MAPK下游基因表达呈正相关(P<0.01)。体内外实验均发现,TC2N表达显著促进ERK与p-ERK表达,且影响ERK相关分子CyclinD1、c-Myc、CDK2和CyclinE1的mRNA和蛋白的表达水平(P<0.01)。结论TC2N基因可能通过激活ERK/MAPK信号通路促进皮肤黑色素瘤的生长。
