Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we i...Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.展开更多
Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing...Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.展开更多
Two methods, rapidly depressurizing to 0.1 MPa at a constant temperature and rising temperature under equilibrium P, T conditions, were used to study the dissociation of pure CH4 hydrate formed below the ice point. At...Two methods, rapidly depressurizing to 0.1 MPa at a constant temperature and rising temperature under equilibrium P, T conditions, were used to study the dissociation of pure CH4 hydrate formed below the ice point. At a constant temperature with rapidly depressurizing to 0.1 MPa, CH4 hydrate dissociated rapidly at initial dissociation and then the dissociation rate gradually decreased. However, the dissociation of CH4 hydrate at temperatures of 261 to 266 K was much faster than that at temperatures of 269 to 272 K, indicating its anomalous preservation. Under an equilibrium P, T conditions, rising temperature had extensively controlling impact on dissociation of CH4 hydrate at equilibrium pressures of 2.31, 2.16 and 1.96 MPa. In this study, we report the effect of pressure on CH4 hydrate dissociation, especially the effect of equilibrium pressure on dissociation at various melting temperatures. And we find that the ice particles size of CH4 hydrate formed may dominant the CH4 hydrate dissociation. Dissociation of CH4 hydrate formed from ice particles of smaller than 250 μm may not have an anomalous preservation below the ice point, while particles larger than 250 μm may have more extensive anomalous preservation.展开更多
Since initially described in 1967, prostatic ductal adenocarcinoma （PDA） has engendered a series of controversies on its origin, histological features, and biological behavior. Owing to the improvement of molecular ...Since initially described in 1967, prostatic ductal adenocarcinoma （PDA） has engendered a series of controversies on its origin, histological features, and biological behavior. Owing to the improvement of molecular biological technique, there are some updated findings on the characteristics of PDA. In the current review, we will mainly analyze its origin, clinical manifestations, morphological features, differential diagnosis, immunophenotype and molecular genetics, with the purpose of enhancing recognition of this tumor and making a correct diagnosis and treatment choice.展开更多
Hypercalcemia presenting in ovarian cancer is uncommon in the clinic.Here,two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported,with a review of the literature.The laboratory...Hypercalcemia presenting in ovarian cancer is uncommon in the clinic.Here,two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported,with a review of the literature.The laboratory findings and stepwise clinical investigations of these two cases differed,indicating distinct underlying causes of hypercalcemia.In case one,the serum levels and immunostaining for parathyroid hormone-related protein(PTHr P)verified humoral hypercalcemia of malignancy(HHM).In case two,the high level of parathyroid hormone(PTH)and the scintigraphy scan showing parathyroid gland adenoma confirmed primary hyperparathyroidism-induced hypercalcemia.Both patients received optimal cytoreductive operation and adjuvant chemotherapy but showed different outcomes respectively.This article focused on differential diagnosis of ovarian cancerassociated hypercalcemia,by stepwise imaging and laboratory investigation,and the appropriate therapy should be considered based on the different etiologies.展开更多
As the most frequent malignant histological subtype in prostatic cancer, prostatic acinar adenocarcinoma （PAA） has a series of benign mimickers including prostatic or non-prostatic lesions and normal structures, whi...As the most frequent malignant histological subtype in prostatic cancer, prostatic acinar adenocarcinoma （PAA） has a series of benign mimickers including prostatic or non-prostatic lesions and normal structures, which may lead to an erroneous diagnosis and inappropriate treatment. It is very important to be aware of the existence of these mimickers and to recognize their histological features. The differential diagnosis should be based on a comprehensive evaluation of clinical history, histological structure, cytological morphology and the results of immunohistochemistry （IHC） straining, rather than on single criteria （e.g., the presence of prominent nueleoli or basal cell layer）.展开更多
Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by red...Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic modifications.However,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains elusive.In this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as inastrocytes.This low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte maturation.However,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in astrocytes.These metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in mice.Moreover,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing glutaminolysis.Finally,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma cells.Collectively,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.展开更多
Animal cloning can be achieved by somatic cell nuclear transfer(SCNT),but the resulting live birth rate is relatively low.We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by ove...Animal cloning can be achieved by somatic cell nuclear transfer(SCNT),but the resulting live birth rate is relatively low.We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by overexpression of lysine-specific demethylase 4D(KDM4D)and 4E(KDM4E).In this study,we revealed abundant alternative splicing(AS)transitions during fertilization and embryonic genome activation,and demonstrated abnormal AS in bovine SCNT embryos compared with in vitro fertilized embryos.We used the CRISPR-Cas13d RNA-targeting system to target cis-elements of ABI2 and ZNF106 pre-m RNA to modify AS,thus reducing the ratio of abnormal-isoform SCNT embryos by nearly 50%and achieving a high survival rate(11%–19%).These results indicate that this system may provide an efficient method for bovine cloning,while also paving the way for further improvements in the efficiency of SCNT.展开更多
基金supported by grants from the National Natural Science Foundation of China (Grant No. 30772316 and 81572568)
文摘Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.
基金supported by grants from the National Natural Science Foundation of China (Grant No.81572568 and 81272863)
文摘Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.
基金supported by the Key Projector of Chinese Academy of Science (No. KZCX-YW-330)the National Science Fund Fostering Talents in Basic Research to Glaciology and Geocryology (Grant No. J0630966)
文摘Two methods, rapidly depressurizing to 0.1 MPa at a constant temperature and rising temperature under equilibrium P, T conditions, were used to study the dissociation of pure CH4 hydrate formed below the ice point. At a constant temperature with rapidly depressurizing to 0.1 MPa, CH4 hydrate dissociated rapidly at initial dissociation and then the dissociation rate gradually decreased. However, the dissociation of CH4 hydrate at temperatures of 261 to 266 K was much faster than that at temperatures of 269 to 272 K, indicating its anomalous preservation. Under an equilibrium P, T conditions, rising temperature had extensively controlling impact on dissociation of CH4 hydrate at equilibrium pressures of 2.31, 2.16 and 1.96 MPa. In this study, we report the effect of pressure on CH4 hydrate dissociation, especially the effect of equilibrium pressure on dissociation at various melting temperatures. And we find that the ice particles size of CH4 hydrate formed may dominant the CH4 hydrate dissociation. Dissociation of CH4 hydrate formed from ice particles of smaller than 250 μm may not have an anomalous preservation below the ice point, while particles larger than 250 μm may have more extensive anomalous preservation.
基金supported by National Natural Science Foundation of China (NSFC 81070582, 81372783 & 81572545)
文摘Since initially described in 1967, prostatic ductal adenocarcinoma （PDA） has engendered a series of controversies on its origin, histological features, and biological behavior. Owing to the improvement of molecular biological technique, there are some updated findings on the characteristics of PDA. In the current review, we will mainly analyze its origin, clinical manifestations, morphological features, differential diagnosis, immunophenotype and molecular genetics, with the purpose of enhancing recognition of this tumor and making a correct diagnosis and treatment choice.
基金supported by National Natural Science Foundation of China (Grant No.81402141)General Project of Science and Technology of Tianjin (Grant No.15JCYBJC26600)
文摘Hypercalcemia presenting in ovarian cancer is uncommon in the clinic.Here,two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported,with a review of the literature.The laboratory findings and stepwise clinical investigations of these two cases differed,indicating distinct underlying causes of hypercalcemia.In case one,the serum levels and immunostaining for parathyroid hormone-related protein(PTHr P)verified humoral hypercalcemia of malignancy(HHM).In case two,the high level of parathyroid hormone(PTH)and the scintigraphy scan showing parathyroid gland adenoma confirmed primary hyperparathyroidism-induced hypercalcemia.Both patients received optimal cytoreductive operation and adjuvant chemotherapy but showed different outcomes respectively.This article focused on differential diagnosis of ovarian cancerassociated hypercalcemia,by stepwise imaging and laboratory investigation,and the appropriate therapy should be considered based on the different etiologies.
基金supported by National Natural Science Foundation of China (NSFC 81070582, 81372783 & 81572545)
文摘As the most frequent malignant histological subtype in prostatic cancer, prostatic acinar adenocarcinoma （PAA） has a series of benign mimickers including prostatic or non-prostatic lesions and normal structures, which may lead to an erroneous diagnosis and inappropriate treatment. It is very important to be aware of the existence of these mimickers and to recognize their histological features. The differential diagnosis should be based on a comprehensive evaluation of clinical history, histological structure, cytological morphology and the results of immunohistochemistry （IHC） straining, rather than on single criteria （e.g., the presence of prominent nueleoli or basal cell layer）.
基金supported by funds from the National Key Research and Development Program of China(2022YFA0806501)the National Natural Science Foundation of China(81972342 to J.Y.,82173120 to Y.G.,and 82070298 to L.Z.)the Natural Science Basic Research Plan in ShaanxiProvince(2020JZ-29 to J.Y.).
文摘Isocitrate dehydrogenase(IDH)mutations frequently occur in lower-grade gliomas and secondary glioblastomas.Mutant IDHs exhibit a gain-of-function activity,leading to the production of D-2-hydroxyglutarate(D-2HG)by reducing α-ketoglutarate(α-KG),a central player in metabolism and epigenetic modifications.However,the role ofα-KG homeostasis in IDH-mutated gliomagenesis remains elusive.In this study,we found that low expression of oxoglutarate dehydrogenase(OGDH)was a common feature in IDH-mutated gliomas,as well as inastrocytes.This low expression of OGDH resultedin the accumulation of α-KG and promoted astrocyte maturation.However,IDH1 mutation significantly reducedα-KG levels and increased glutaminolysis and DNA/histone methylation in astrocytes.These metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in mice.Moreover,our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells,while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation ofα-KG and increasing glutaminolysis.Finally,we found that l-glutamine increasedα-KG levels and augmented the differentiation-promoting effects of AGI5198,an IDH1-mutant inhibitor,in IDH1-mutant glioma cells.Collectively,this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas,providing a potential strategy for the treatment of IDH-mutant gliomas by targetingα-KG homeostasis.
基金the National Natural Science Foundation of China(31802153,32072805 and 31872539)Special Funds for Talents in Northwest A&F University(Z111021512 and Z109021702)+1 种基金Innovation Project of Science and Technology in Shaanxi Province(2018JQ3035)National Major Project for Production of Transgenic Breeding(2016ZX08007-003)。
文摘Animal cloning can be achieved by somatic cell nuclear transfer(SCNT),but the resulting live birth rate is relatively low.We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by overexpression of lysine-specific demethylase 4D(KDM4D)and 4E(KDM4E).In this study,we revealed abundant alternative splicing(AS)transitions during fertilization and embryonic genome activation,and demonstrated abnormal AS in bovine SCNT embryos compared with in vitro fertilized embryos.We used the CRISPR-Cas13d RNA-targeting system to target cis-elements of ABI2 and ZNF106 pre-m RNA to modify AS,thus reducing the ratio of abnormal-isoform SCNT embryos by nearly 50%and achieving a high survival rate(11%–19%).These results indicate that this system may provide an efficient method for bovine cloning,while also paving the way for further improvements in the efficiency of SCNT.
