促纤维增生性小圆细胞肿瘤(desmoplastic small round cell tumor,DSRCT)为一种极罕见、高度恶性的软组织肉瘤。除偶然发现外,多数患者确诊时已为晚期。DSRCT主要发生于腹盆腔,沿腹膜表面播散,多数患者确诊时已失去手术机会。DSRCT的诊...促纤维增生性小圆细胞肿瘤(desmoplastic small round cell tumor,DSRCT)为一种极罕见、高度恶性的软组织肉瘤。除偶然发现外,多数患者确诊时已为晚期。DSRCT主要发生于腹盆腔,沿腹膜表面播散,多数患者确诊时已失去手术机会。DSRCT的诊断是基于组织学检查,典型的表现为癌巢中的小圆蓝色细胞被大量的纤维增生性基质分隔开。特征性的t(11;22)(p13;q12)染色体异位产生EWSR1-WT1融合基因是DSRCT稳定存在的遗传学特点。该病预后极差,5年生存率仅约15%,主要由于肿瘤发生转移所致。DSRCT的治疗仍然具有挑战性,尽管使用了积极的治疗方法,如化疗、手术和全腹部放疗等,但60%~70%患者在2~3年内死亡。随着对DSRCT分子遗传学的研究不断深入,靶向治疗、免疫治疗等方法近年开始尝试应用于DSRCT的治疗。展开更多
RAD9 regulates multiple cellular processes that influence genomic integrity,and for at least some of its functions the protein acts as part of a heterotrimeric complex bound to HUS1 and RAD1 proteins.RAD9 participates...RAD9 regulates multiple cellular processes that influence genomic integrity,and for at least some of its functions the protein acts as part of a heterotrimeric complex bound to HUS1 and RAD1 proteins.RAD9 participates in DNA repair,including base excision repair,homologous recombination repair and mismatch repair,multiple cell cycle phase checkpoints and apoptosis.In addition,functions including the transactivation of downstream target genes,immunoglobulin class switch recombination,as well as 3′–5′exonuclease activity have been reported.Aberrant RAD9 expression has been linked to breast,lung,thyroid,skin and prostate tumorigenesis,and a cause–effect relationship has been demonstrated for the latter two.Interestingly,human RAD9 overproduction correlates with prostate cancer whereas deletion of Mrad9,the corresponding mouse gene,in keratinocytes leads to skin cancer.These results reveal that RAD9 protein can function as an oncogene or tumor suppressor,and aberrantly high or low levels can have deleterious health consequences.It is not clear which of the many functions of RAD9 is critical for carcinogenesis,but several alternatives are considered herein and implications for the development of novel cancer therapies based on these findings are examined.展开更多
文摘促纤维增生性小圆细胞肿瘤(desmoplastic small round cell tumor,DSRCT)为一种极罕见、高度恶性的软组织肉瘤。除偶然发现外,多数患者确诊时已为晚期。DSRCT主要发生于腹盆腔,沿腹膜表面播散,多数患者确诊时已失去手术机会。DSRCT的诊断是基于组织学检查,典型的表现为癌巢中的小圆蓝色细胞被大量的纤维增生性基质分隔开。特征性的t(11;22)(p13;q12)染色体异位产生EWSR1-WT1融合基因是DSRCT稳定存在的遗传学特点。该病预后极差,5年生存率仅约15%,主要由于肿瘤发生转移所致。DSRCT的治疗仍然具有挑战性,尽管使用了积极的治疗方法,如化疗、手术和全腹部放疗等,但60%~70%患者在2~3年内死亡。随着对DSRCT分子遗传学的研究不断深入,靶向治疗、免疫治疗等方法近年开始尝试应用于DSRCT的治疗。
基金supported by National Institutes of Health grants CA130536,CA049062,ES017557 and GM079107.
文摘RAD9 regulates multiple cellular processes that influence genomic integrity,and for at least some of its functions the protein acts as part of a heterotrimeric complex bound to HUS1 and RAD1 proteins.RAD9 participates in DNA repair,including base excision repair,homologous recombination repair and mismatch repair,multiple cell cycle phase checkpoints and apoptosis.In addition,functions including the transactivation of downstream target genes,immunoglobulin class switch recombination,as well as 3′–5′exonuclease activity have been reported.Aberrant RAD9 expression has been linked to breast,lung,thyroid,skin and prostate tumorigenesis,and a cause–effect relationship has been demonstrated for the latter two.Interestingly,human RAD9 overproduction correlates with prostate cancer whereas deletion of Mrad9,the corresponding mouse gene,in keratinocytes leads to skin cancer.These results reveal that RAD9 protein can function as an oncogene or tumor suppressor,and aberrantly high or low levels can have deleterious health consequences.It is not clear which of the many functions of RAD9 is critical for carcinogenesis,but several alternatives are considered herein and implications for the development of novel cancer therapies based on these findings are examined.
