卵巢癌基因1(ovarian cancer gene 1,OVCA1)位于人染色体17p13.3,在哺乳动物细胞中高度保守,与酵母菌的DPH2具有同源性。在哺乳动物细胞中,OVCA1参与维持翻译的保真性、调控细胞周期及胚胎发育等多种生物学过程。OVCA1在卵巢癌、乳腺癌...卵巢癌基因1(ovarian cancer gene 1,OVCA1)位于人染色体17p13.3,在哺乳动物细胞中高度保守,与酵母菌的DPH2具有同源性。在哺乳动物细胞中,OVCA1参与维持翻译的保真性、调控细胞周期及胚胎发育等多种生物学过程。OVCA1在卵巢癌、乳腺癌和宫颈癌等多种肿瘤中存在高频率的杂合性缺失和突变,作为候选肿瘤抑制基因在肿瘤发生发展中发挥重要作用。本文就OVCA1基因的生物学功能及与不同类型肿瘤关系的研究进展做一综述。展开更多
Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading cause...Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis.Studies have explored the influence of ER stress on OvCa in recent years,while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored.Here,we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)cohorts for the screening of prognosis-related genes.The least absolute shrinkage and selection operator(LASSO)regression was applied to establish an ER stress-related risk signature based on the TCGA cohort.A seven-gene signature revealed a favorable predictive efficacy for the TCGA,International Cancer Genome Consortium(ICGC),and another GEO cohort(P<0.001,P<0.001,and P=0.04,respectively).Moreover,functional annotation indicated that this signature was enriched in cellular response and senescence,cytokines interaction,as well as multiple immune-associated terms.The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group.In conclusion,ER stress-related genes are vital factors predicting the prognosis of OvCa,and possess great application potential in the clinic.展开更多
The recent publication by Mollaoglu et al.1 in Cell reveals an unexpected role for tumor derived IL4 in driving immunotherapy resistance in ovarian cancer(OvCa).This finding nominates the combination of immunotherapy ...The recent publication by Mollaoglu et al.1 in Cell reveals an unexpected role for tumor derived IL4 in driving immunotherapy resistance in ovarian cancer(OvCa).This finding nominates the combination of immunotherapy and IL4-signaling targeting strategies as a promising new approach for the treatment of advanced OvCa.Ovarian Cancer(OvCa)is the third most common gynecological malignant disease affecting women.2 It is often diagnosed at late stages and is characterized by heterogenous features with limited treatment options.Initial response to standard of care platinumbased chemotherapy combined with surgery is often followed by disease relapse and subsequent death of patients.Despite the recent success of immune checkpoint inhibition in different cancer entities,most OvCa patients do not benefit from immunotherapy-based treatment approaches.The responsiveness of ovarian tumors to immune checkpoint blockade(ICB)is thereby hindered by weak immunogenicity due to low mutational burden and an immune suppressive tumor microenvironment(TME)characterized by heterogenous immune cell infiltration.3 Still,functional evidence for key factors that govern cancer cellimmune cell interaction and drive immunotherapy resistance in OvCa remains limited.展开更多
There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSC...There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSCs existed in human ovarian cancer (OVCA) cell line and whether anti-CD44 antibody had effects on such subpopulation. We isolated and identified spheroid cells from SKOV-3. Then we used A3D8, an anti-CD44 mAb to treat spheroid cells with so-called "stemness". Effects of A3D8 on spheroid cells' biological behaviors were examined. Our findings showed that there was a small subpopulation that had so-called "stemness" in SKOV-3 cell line. Against spheroid cells, A3D8 can (1) inhibit cell proliferation; (2) change cell cycle distribution and expression of p21, CDK2 and cyclinA; (3) enhance cisplatin (DDP)-induced apoptosis; (4) promote cell differentiation; (5) inhibit clone formation efficiency; (6) reduce invasive efficacy; (7) inhibit tumorigenicity. Thus, to sum up points which we have just showed, spheroid cells isolated from SKOV-3 can be used as an appropriate in vitro model for relevant study of human ovarian CSCs. And our results reasoned that anti-CD44 therapy may become a potential promising strategy for OVCA treatment.展开更多
文摘卵巢癌基因1(ovarian cancer gene 1,OVCA1)位于人染色体17p13.3,在哺乳动物细胞中高度保守,与酵母菌的DPH2具有同源性。在哺乳动物细胞中,OVCA1参与维持翻译的保真性、调控细胞周期及胚胎发育等多种生物学过程。OVCA1在卵巢癌、乳腺癌和宫颈癌等多种肿瘤中存在高频率的杂合性缺失和突变,作为候选肿瘤抑制基因在肿瘤发生发展中发挥重要作用。本文就OVCA1基因的生物学功能及与不同类型肿瘤关系的研究进展做一综述。
基金This work was supported by the Shanghai Shenkang Hospital Development Center’s Shenkang Promotion of Clin‑ical Skills and Clinical Innovation in Municipal Hospitals Three-Year Action Plan(No.2020‒2023)the Major Clinical Research Project(No.SHDC2020CR1048B)the Pilot Construction Project of High-Level Universities in Shanghai(No.DGF501017-06),China。
文摘Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis.Studies have explored the influence of ER stress on OvCa in recent years,while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored.Here,we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)cohorts for the screening of prognosis-related genes.The least absolute shrinkage and selection operator(LASSO)regression was applied to establish an ER stress-related risk signature based on the TCGA cohort.A seven-gene signature revealed a favorable predictive efficacy for the TCGA,International Cancer Genome Consortium(ICGC),and another GEO cohort(P<0.001,P<0.001,and P=0.04,respectively).Moreover,functional annotation indicated that this signature was enriched in cellular response and senescence,cytokines interaction,as well as multiple immune-associated terms.The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group.In conclusion,ER stress-related genes are vital factors predicting the prognosis of OvCa,and possess great application potential in the clinic.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation,LE 3613/3-1).
文摘The recent publication by Mollaoglu et al.1 in Cell reveals an unexpected role for tumor derived IL4 in driving immunotherapy resistance in ovarian cancer(OvCa).This finding nominates the combination of immunotherapy and IL4-signaling targeting strategies as a promising new approach for the treatment of advanced OvCa.Ovarian Cancer(OvCa)is the third most common gynecological malignant disease affecting women.2 It is often diagnosed at late stages and is characterized by heterogenous features with limited treatment options.Initial response to standard of care platinumbased chemotherapy combined with surgery is often followed by disease relapse and subsequent death of patients.Despite the recent success of immune checkpoint inhibition in different cancer entities,most OvCa patients do not benefit from immunotherapy-based treatment approaches.The responsiveness of ovarian tumors to immune checkpoint blockade(ICB)is thereby hindered by weak immunogenicity due to low mutational burden and an immune suppressive tumor microenvironment(TME)characterized by heterogenous immune cell infiltration.3 Still,functional evidence for key factors that govern cancer cellimmune cell interaction and drive immunotherapy resistance in OvCa remains limited.
基金supported by the National Natural Science Foundation of China (30670801)the Tianjin Research Program of Application Foundation and Advanced Technology (06YFJMJC08300)
文摘There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSCs existed in human ovarian cancer (OVCA) cell line and whether anti-CD44 antibody had effects on such subpopulation. We isolated and identified spheroid cells from SKOV-3. Then we used A3D8, an anti-CD44 mAb to treat spheroid cells with so-called "stemness". Effects of A3D8 on spheroid cells' biological behaviors were examined. Our findings showed that there was a small subpopulation that had so-called "stemness" in SKOV-3 cell line. Against spheroid cells, A3D8 can (1) inhibit cell proliferation; (2) change cell cycle distribution and expression of p21, CDK2 and cyclinA; (3) enhance cisplatin (DDP)-induced apoptosis; (4) promote cell differentiation; (5) inhibit clone formation efficiency; (6) reduce invasive efficacy; (7) inhibit tumorigenicity. Thus, to sum up points which we have just showed, spheroid cells isolated from SKOV-3 can be used as an appropriate in vitro model for relevant study of human ovarian CSCs. And our results reasoned that anti-CD44 therapy may become a potential promising strategy for OVCA treatment.
