1.Research progress in and new treatment strategies for melanoma in China
Chinese Journal of Dermatology 2021;54(1):27-32
Although the incidence of melanoma is increasing rapidly, its proportion is relatively low among all the malignant tumors in China, and oncologists commonly pay little attention. The first consultation place for melanoma patients is mainly the department of dermatology. Dermatologists have unique advantages in the diagnosis and treatment of melanoma since they can comprehensively integrate clinical diagnosis, pathological diagnosis, surgical treatment and drug treatment. In recent years, Chinese scholars have made great progress in melanoma research, such as regulation of cell death, epigenetic modification, resistance to targeted drugs, tumor microenvironment and tumor immune regulation. Interferon α-1b, a unique new drug in China, not only can be used for adjuvant treatment of high-risk stage Ⅱ and Ⅲ melanoma, but also shows good efficacy in the treatment of stage Ⅳ melanoma, and adverse reactions to it are far less than those to interferon α-2b. Unlike the White population, the common subtypes of melanoma are acral and mucosal melanomas in the Asian population. The combination of interferon α-1b with programmed death receptor-ligand 1 inhibitor, targeted drugs or angiogenesis inhibitors is bringing hope for patients with stage IV melanoma.
2.Application of the PD-1 antibody in melanoma therapy
Yanhong ZHAO ; Pu SONG ; Tianwen GAO
Chinese Journal of Clinical Oncology 2016;43(13):589-592
A melanoma is a highly malignant tumor that originates from melanocytes in the skin, mucosa, or tunica pigmentosa. The incidence and mortality rate of cutaneous melanoma are increasing annually. However, the efficacy of traditional therapy is extremely limited because of its low sensitivity and high toxicity. The application of the anti-CTLA-4 antibody and the BRAF inhibitor dramatically improves the overall survival of patients with advanced melanoma. However, their limited benefit ratio and high drug resistance curtail the use of anti-CTLA-4. Since the US Food and Drug Administration approved the use of the anti-PD-1 and anti-PD-L1 antibodies for ad-vanced melanoma in 2014, a significant survival benefit has been observed in patients with advanced melanoma. This review aims to highlight the applications of the anti-PD-1 antibody (pembrolizumab, nivolumab, and pidilizumab) and the anti-PD-L1 antibody (MP-DL3280A, BMS-936559, and MEDI4736) in the clinical treatment of melanoma by succinctly summarizing the results of recent reports.
3.Detection of Auto Antibodies to Melanocyte Surface Antigen in Sera of Patients with Vitiligo
Zhiqiang LI ; Tianwen GAO ; Xiaodong ZHAO
Chinese Journal of Dermatology 1995;0(04):-
Objective To detect circulating autoantibodies to melanocytes in patients with vitiligo and its relationship to disease activity and subtypes. Methods IgG autoantibodies to melanocyte surface antigens were measured in sera from 334 patients with vitiligo and 50 normal individuals using a live cell enzyme linked immunoabsorbent assay. Results Anti melanocyte IgG antibody was present in 67% of patients(165/250) with active non segmental vitiligo, 30.3% of patients(10/33) with inactive non segmental vitiligo, 40.54% of patients(23/51) with active segmental vitiligo and 21.42% of patients with inactive segmental vitiligo (3/14). The autoantibody levels were significantly higher in patients with active non segmental vitiligo and active segmental vitiligo than those with inactive disease or normal individuals. Conclusion Autoimmune mechanism may play an important role in both non segmental and segmental vitiligo.
4.Significance of aberrant melanosomes in the diagnosis of malignant melanoma
Tianwen GAO ; Qingyi YE ; Rongqing LIU
Journal of Third Military Medical University 1983;0(04):-
Seventeen cases of malignant melanoma (MM) were observed with transmission electron microscopy in order to clarify the significance of abberant melanosomes in its diagnosis.30 cases of nevus were also studied to serve as control.It was found that aberrant melanosomes were present in 14 cases of MM including 2 cases of amelanotic MM and absent in 2 cases of pigmented MM and one case of amelanotic MM.In addition,aberrant melanosomes were found in 4 cases of congenital nevus.The findings suggest that the significance of aberrant melanosomes in the diagnosis of MM has been overemphasized.It is believed that the diagnosis of MM must be judged comprehensively on all the ultrastructural changes under transmission electron microscope.
5.The significance of congenital small nevus in the pathogenesis of malignant melanoma
Tianwen GAO ; Rongqing LIU ; Qingyi YE
Journal of Third Military Medical University 1988;0(05):-
There are controversies concerning whether congential small nevus(CSN)is liable to undergo malignant degeneration and whether it should be resected promptly.The signif-icane of CSN in the pathogenesis of malignant melanoma(MM)was assessed with microspec-trophotometric determination of DNA quantity,the detection of the gene product of N-ras,p21 protein,with ABC technique,ultrastructural study of MM tissue with electron microscopy,and analysis of clinical data of MM.The findings were as follows:(1)The DNA content increased sequentially in order of acquired nevus(AN),CSN,congenital giant nevus(CGN)and MM,and the difference was statistically significant among the 4 groups(P
6.Expression of ?-Catenin and LEF-1 in Malignant Melanoma
Hehui YIN ; Wenjun LIAO ; Ying GAO ; Tianwen GAO
Chinese Journal of Dermatology 2003;0(11):-
Objective To investigate ?-catenin and lymphoid enhancing factor 1 (LEF-1) expression in malignant melanoma. Methods ?-catenin and LEF-1 protein expression was examined using the PowerVisionTM immunohistochemical method in 25 cases of intradermal nevus and 45 cases of malignant melanoma. Results Comparing malignant melanoma with intradermal nevi, there was a significant difference in the expression of ?-catenin (33/45= 73% vs. 9/25 = 36%, respectively; P
7.Expression of Double-stranded RNA-dependent Protein Kinase in Malignant Melanoma and Ordinary Nevi
Ying GAO ; Chunying LI ; Cuiling MA ; Hehui YIN ; Tianwen GAO
Chinese Journal of Dermatology 2003;0(12):-
Objective To study the expression of double-stranded RNA-dependent protein kinase (PKR) in malignant melanoma and ordinary nevi. Methods The expression of PKR and proliferating cell nuclear antigen was examined in 42 cases of malignant melanoma and 25 ordinary nevi by an immunohistochemical method. Results The positive rate of PKR expression was higher in the patients with malignant melanoma than that in the patients with ordinary nevi (P
8.Relationship between the functional single nucleotide polymorphism rs1052133 in the 8-oxoguanine DNA glycosylase 1 (OGG1) gene and vitiligo in a Chinese Han population
Chao WEI ; Huini QIANG ; Tianwen GAO ; Chunying LI
Chinese Journal of Dermatology 2013;(4):227-230
Objective To estimate the relationship of the functional single nucleotide polymorphism (SNP) rs1052133 in the 8-oxoguanine DNA glycosylase 1 (OGG1) gene with vitiligo in a Chinese Han population.Methods Blood samples were collected from 800 patients with vitiligo and 800 healthy human controls,and subjected to genomic DNA extraction.PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the genotype of the SNP rs1052133 in the OGG1 gene.The relationship between the SNP and the risk of vitiligo was evaluated by chi-square test and unconditional logistic regression analysis.Enzyme linked immunosorbent assay (ELISA) was carried out to assess the serum level of 8-hydroxydeoxyguanosine (8-OHdG) in 83 patients with vitiligo and 83 healthy human controls,then,t test was used to compare the serum 8-OHdG level between the patients and controls.Results The frequency of CC,CG and GG genotype of the SNP rs1052133 was 16.8%,54.0% and 29.2% respectively in the patients,21.4%,52.8% and 25.8%respectively in the controls (x2 =6.26,P < 0.05).Increased frequency of G allele of the SNP rs1052133 was observed in the patients with vitiligo compared with the controls (56.2% vs.52.2%,x2 =5.16,P < 0.05).A statistically increased risk of vitiligo was associated with the CG (x2 =3.98,P < 0.05,adjusted odds ratio 1.31,95% confidence interval:1.01-1.70) and GG (x2 =6.01,P < 0.05,adjusted odds ratio 1.45,95% confidence interval:1.08-1.94) genotype of SNP rs1052133 compared with the CC genotype,which was more evident among the patients with the following characteristics:female,nonsegmental vitiligo,active vitiligo,long clinical course (> 12 months),a family history of vitiligo,and no accompanied autoimmune diseases.In addition,the patients with the CG or GG genotype of SNP rs1052133 had a higher serum 8-OHdG level than those with the CC genotype ((838.23 ± 294.11) μg/L vs.(593.84 ± 190.14) μg/L,t =3.63,P < 0.01).Conclusions The SNP rs1052133 in the OGG1 gene may be responsible for the development of vitiligo in Chinese Han populations,which is likely to be associated with defects in DNA repair.
9.The Inhibition of Antisense TRPl in the Proliferation of Malignant Melanoma Cells in vivo and in vitro
Chunying LI ; Tianwen GAO ; Xianlong QI ; Gang WANG ; Yufeng LIU
Chinese Journal of Cancer Biotherapy 1996;0(04):-
Objective: To study the inhibition of antisense TRP1 on cell growth of malignant melanoma(MM) and explore a new way for therapy of melanoma. Methods: Antisense TRP-1 recombinant vector was constructed and transfected into MM cells. According to the results of MTT, cell growth curves were drawn and then clonogenic assay was performed in vitro. At last, tumorigenesis assay was undertaken in nude mice in vivo. Results: Cell proliferations of TRP-1 transfected MM cells were inhibited compared with the control cells. The results of clonogenic assay displayed the difference of clonogenic percentage between TRP-1 transfected MM cells (52% , P
10.Downregulation of K14 Genes and Protein Expression by Liposome Conjugated Antisense Oligonucleotides in Keratinocytes
Yuxin CHEN ; Wei LI ; Jianyong FAN ; Yufeng LIU ; Tianwen GAO
Chinese Journal of Dermatology 1995;0(04):-
Objective To probe into the gene therapy of psoriasis using antisense oligonucleotides to attenuate the expression of K14 gene and protein in keratinocytes and evaluate the inhibitory effects of liposome conjugated antisense oligonucleotides on the proliferation of keratinocytes. Methods The antisense, sense and mismatched oligonucleotides for K14 gene were synthesized and conjugated with lipofectin respectively. Finally they were subsequently transfected into cultured keratinocytes in vitro. The expression of K14 gene was tested by reverse transcription polymerase chain reaction (RT-PCR). The expression of K14 protein was measured by immunohistochemistry. The variation of cell growth cycle was detected by flow cytometry. Results The expression of K14 gene and protein was markedly decreased in keratinocytes treated with K14 antisense oligonucleotides. The cell growth cycle was inhibited effectively by antisense oligonucleotides with lipofection, but not by sense and mismatched oligonucleotides. Conclusions Antisense oligonucleotides conjugated with lipofectin might be a hopeful method to inhibit the proliferation of keratinocytes by inhibiting the expression of K14 mRNA and protein.