Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is ch...Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired chemoresistance.Cancer stem cell(CSC)theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and tumor-initiation.The most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth,metastasis and relapse of disease,but also for the development of chemoresistance.As the elimination of this cell population is critical for increasing treatment success,a deeper understanding of ovarian CSCs pathobiology,including epithelial-mesenchymal transition,signaling pathways and tumor microenvironment,is needed.Finally,before introducing new therapeutic agents for ovarian cancer,targeting CSCs,accurate identification of different ovarian stem cell subpopulations,including the very small embryoniclike stem cells suggested as progenitors,is necessary.To these ends,reliable markers of ovarian CSCs should be identified.In this review,we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role.展开更多
Chemotherapeutic agents are extensively used to treat malignancies.However,chemotherapy-induced ovarian damage and reduced fertility are severe side effects.Recently,stem cell transplantation has been reported to be a...Chemotherapeutic agents are extensively used to treat malignancies.However,chemotherapy-induced ovarian damage and reduced fertility are severe side effects.Recently,stem cell transplantation has been reported to be an effective strategy for premature ovarian insufficiency(POI)treatment,but safety can still be an issue in stem cell-based therapy.Here,we show the protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium(hUCMSC-CM)on a cisplatin(Cs)-induced ovarian injury model.hUCMSC-CM can relieve Cs-induced depletion of follicles and preserve fertility.In addition,hUCMSC-CM can decrease apoptosis of oocytes and granulosa cells induced by Cs.RNA sequencing analysis reveals the differentially expressed genes of ovaries after Cs and hUCMSC-CM treatments,including genes involved in cell apoptosis.Furthermore,we show that the granulocyte colony-stimulating factor(G-CSF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway plays an important role in protecting granulosa cells from Cs-induced apoptosis.Together,we confirm the protective effects of hUCMSC-CM on ovarian reserve and fertility in mice treated with Cs,highlighting the remarkable therapeutic effects of hUCMSC-CM.展开更多
Female reproduction and health are highly dependent on ovarian function.Ovarian reserve is a critical indicator of ovarian function[1].The ovarian reserve refers to the stock of dormant primordial follicles(primordial...Female reproduction and health are highly dependent on ovarian function.Ovarian reserve is a critical indicator of ovarian function[1].The ovarian reserve refers to the stock of dormant primordial follicles(primordial follicle pool)residing in the ovarian cortex[2].The primordial germ cells(PGCs)are enclosed by the basal lamina to form cyst at the beginning of ovarian development[3].展开更多
Diminished ovarian reserve(DOR),generally defined as a decreased number or quality of oocytes,has a significant impact on quality of life and fertility in women.In recent years,the incidence of DOR has been increasing...Diminished ovarian reserve(DOR),generally defined as a decreased number or quality of oocytes,has a significant impact on quality of life and fertility in women.In recent years,the incidence of DOR has been increasing and the ages of patients are younger.The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health.An effective DOR therapy would improve ovarian function,fertility,and quality of life in patients.In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine,and elucidated the characteristics of each treatment.展开更多
文摘Ovarian cancer is the deadliest gynecological malignancy.It is typically diagnosed at advanced stages of the disease,with metastatic sites disseminated widely within the abdominal cavity.Ovarian cancer treatment is challenging due to high disease recurrence and further complicated pursuant to acquired chemoresistance.Cancer stem cell(CSC)theory proposes that both tumor development and progression are driven by undifferentiated stem cells capable of self-renewal and tumor-initiation.The most recent evidence revealed that CSCs in terms of ovarian cancer are not only responsible for primary tumor growth,metastasis and relapse of disease,but also for the development of chemoresistance.As the elimination of this cell population is critical for increasing treatment success,a deeper understanding of ovarian CSCs pathobiology,including epithelial-mesenchymal transition,signaling pathways and tumor microenvironment,is needed.Finally,before introducing new therapeutic agents for ovarian cancer,targeting CSCs,accurate identification of different ovarian stem cell subpopulations,including the very small embryoniclike stem cells suggested as progenitors,is necessary.To these ends,reliable markers of ovarian CSCs should be identified.In this review,we present the current knowledge and a critical discussion concerning ovarian CSCs and their clinical role.
基金supported by grants from the National Key Research and Development Program(2017YFA0103800 and 2019YFA0110901)the National Natural Science Foundation of China(81471431,81871133,81672085,and 31501102)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201830).
文摘Chemotherapeutic agents are extensively used to treat malignancies.However,chemotherapy-induced ovarian damage and reduced fertility are severe side effects.Recently,stem cell transplantation has been reported to be an effective strategy for premature ovarian insufficiency(POI)treatment,but safety can still be an issue in stem cell-based therapy.Here,we show the protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium(hUCMSC-CM)on a cisplatin(Cs)-induced ovarian injury model.hUCMSC-CM can relieve Cs-induced depletion of follicles and preserve fertility.In addition,hUCMSC-CM can decrease apoptosis of oocytes and granulosa cells induced by Cs.RNA sequencing analysis reveals the differentially expressed genes of ovaries after Cs and hUCMSC-CM treatments,including genes involved in cell apoptosis.Furthermore,we show that the granulocyte colony-stimulating factor(G-CSF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway plays an important role in protecting granulosa cells from Cs-induced apoptosis.Together,we confirm the protective effects of hUCMSC-CM on ovarian reserve and fertility in mice treated with Cs,highlighting the remarkable therapeutic effects of hUCMSC-CM.
基金supported by the National Key R&D Program of China(2018YFE0201100 and 2019YFA0110900)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16021400)+2 种基金CAMS Innovation Fund for Medical Sciences(2016-I2M-1-001)Beijing Hospitals Authority’Ascent Plan(DFL20191401)the National Natural Science Foundation of China(81871133)。
文摘Female reproduction and health are highly dependent on ovarian function.Ovarian reserve is a critical indicator of ovarian function[1].The ovarian reserve refers to the stock of dormant primordial follicles(primordial follicle pool)residing in the ovarian cortex[2].The primordial germ cells(PGCs)are enclosed by the basal lamina to form cyst at the beginning of ovarian development[3].
基金Supported by the Fund for Beijing Science&Technology Development of Traditional Chinese Medicine(No.JJ-2018-73)。
文摘Diminished ovarian reserve(DOR),generally defined as a decreased number or quality of oocytes,has a significant impact on quality of life and fertility in women.In recent years,the incidence of DOR has been increasing and the ages of patients are younger.The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health.An effective DOR therapy would improve ovarian function,fertility,and quality of life in patients.In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine,and elucidated the characteristics of each treatment.