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
The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant gliom...The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.展开更多
Background:Pleomorphic xanthoastrocytoma (PXA) is usually considered a relatively benign and localized entity. However, cases of PXA with anaplastic features have been reported in recent years. Anaplastic pleomorphic ...Background:Pleomorphic xanthoastrocytoma (PXA) is usually considered a relatively benign and localized entity. However, cases of PXA with anaplastic features have been reported in recent years. Anaplastic pleomorphic xanthoastrocytoma has been added to the 2016 WHO classification of CNS tumors as a distinct entity. Case presentation:We describe a rare case of PXA with dissemination, both at the time of diagnosis and after treatment. The 20-year-old male presented with signs of high intracranial pressure and sudden-onset transient seizures. Imaging examinations showed diffuse lesions widely distributed in the left hemisphere, and on histopathological examination, he was diagnosed with anaplastic PXA. The patient underwent surgical treatment and adjuvant concurrent chemoradiation. Follow-up MRI revealed early recurrence and distant spread of the tumor. Conclusions:Anaplastic PXA usually has unique characteristics, including dissemination, early recurrence, and chemoresistance. A strategy based on early diagnosis and aggressive treatment is warranted. However, sufficiently powered studies are required to generate evidence-based guidelines.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 the National Natural Science Foundation of China(30770827,31170864and81100887)National Basic Research Development Program of China(973Program,2010CB529405)+5 种基金Key Laboratory Project of Tianjin Municipality for Science and Technology(10SYSYJC28800)Major Program of Research on Applied Fundamentals and Frontier Technologies(10JCZDJC19400)Key Program of Higher Education of Tianjin Municipality for Science and Technology(2004ZD06,20060202)Program for New Century Excellent Talents in University of China(NCET-11-1067)Key Project of Natural Science Foundation of Tianjin Municipality,China(12JCZDJC24200)Key Project for Science and Technology of Ministry of Education,China(212005)
文摘The matrix-degrading metalloproteinases （MMPs）, particularly MMP-9, play important roles in the pathogenesis and development of malignant gliomas. In the present study, the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo. TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA （pcDNA-AS-MMP9）, which significantly decreased MMP-9 expression, and cell proliferation was assessed. For in vivo studies, U251 cells, a human malignant glioma cell line, were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice. The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex （AS-MMP-9-treated group）, subcutaneous injection of endostatin （endostatin-treated group）, or both （combined therapy group）. Mice treated with pcDNA （empty vector）-Lipofectamine served as the control group. Four or eight weeks later, the volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity were assayed. We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation. Volume and weight of tumor, MMP-9 expression, microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group. The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness, but also affects tumor cell proliferation. Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells, and thus can be used as an effective therapeutic strategy for malignant gliomas.
基金We thank grants from the the National Natural Science Foundation of China，the Specialized Research Fund for the Doctoral Program of Higher Education (no. 20131202110006). Both of the two fundings were based on the comprehensive therapy of glioma
文摘Background:Pleomorphic xanthoastrocytoma (PXA) is usually considered a relatively benign and localized entity. However, cases of PXA with anaplastic features have been reported in recent years. Anaplastic pleomorphic xanthoastrocytoma has been added to the 2016 WHO classification of CNS tumors as a distinct entity. Case presentation:We describe a rare case of PXA with dissemination, both at the time of diagnosis and after treatment. The 20-year-old male presented with signs of high intracranial pressure and sudden-onset transient seizures. Imaging examinations showed diffuse lesions widely distributed in the left hemisphere, and on histopathological examination, he was diagnosed with anaplastic PXA. The patient underwent surgical treatment and adjuvant concurrent chemoradiation. Follow-up MRI revealed early recurrence and distant spread of the tumor. Conclusions:Anaplastic PXA usually has unique characteristics, including dissemination, early recurrence, and chemoresistance. A strategy based on early diagnosis and aggressive treatment is warranted. However, sufficiently powered studies are required to generate evidence-based guidelines.
