AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 a...AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS: All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% ± 2.4% (mean ± SD), 30.9% ± 5.5%, 23.8% ± 3.9%, 37.1% ± 5.3%, 10.4% ± 4.5%, 52.5% ± 4.5% and 22.6% ± 0.4%, at 2 μmol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% ± 7.6%, 32.9% ± 8.2%, 53.9% ± 8.0%, 52.8% ± 4.0%, 32.3% ± 4.2%, 51.8% ± 4.5%, and 30.6% ± 9.4%, at 50 μmol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% ± 0.2%, 0%, 0%, 2.0% ± 0.1%, 5.0% ± 0.2%, 3.0% ± 0.1%, and 5.0% ± 0.2%, respectively (P < 0.05). LY294002 at 50 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% ± 0.2%, 0%, 3.0% ± 0.2%, 0%, 0%, 0% and 3% ± 0.1%, respectively (P < 0.05). PD980509 at 20 μmol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 μmol/L PPP or 50 μmol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 μmol/L PD98059 did not show apoptosis.CONCLUSION: IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer.展开更多
Background Hyperinsulinemia, insulin-like growth factor （IGF）-I and -Ⅱ （IGF-Ⅱ） are associated with increased risk of endometrial carcinoma. Insulin receptor isoform A （IR-A） is more frequently expressed in end...Background Hyperinsulinemia, insulin-like growth factor （IGF）-I and -Ⅱ （IGF-Ⅱ） are associated with increased risk of endometrial carcinoma. Insulin receptor isoform A （IR-A） is more frequently expressed in endombtrial carcinoma than in normal endometrial tissues. To better understand their roles in endometrial carcinoma, we investigated the effects of insulin, IGF-I, and IGF-II in endometrial carcinomas cells with different IR-A expression levels. Methods To explore the role of IR-A in mediating the activity of IGF-I, IGF-II, and insulin, we investigate the cellular proliferation of endometrial carcinoma cell lines RL95-2 and RL95-2-1R-A by MTS assays. Then we examined the protein kinase Akt phosphorylation and extracellular signal-regulated kinase （ERK） 1/2 phosphorylation in both cell lines by Western blotting. The effect of IGF-II and AG1024 on cell cycle progression and apoptosis was assessed by fiowcytometry. To examine whether the effects of IGFs were mediated by IR-A, we blocked IGF-I receptor （IGF-IR） in both cell lines using AG1024, an IGF-IR-specific inhibitor. Results IGF-I and IGF-II significantly enhanced proliferation of both cell lines （P 〈0.05）. By contrast, insulin significantly increased proliferation of RL95-2-1R-A cells only （P 〈0.05）. IGF-I and IGF-II significantly increased pAkt levels in RL95-2 cells and pERK1/2 levels in RL95-2-1R-A cells （all, P 〈0.05）. Insulin increased pERK1/2 levels in RL95-2-1R-A cells only （P 〈0.05）. LY294002 and PD98059 inhibited the specific signaling activities and cellular proliferation. After AG1024 pretreatment, neither IGF-I nor IGF-II affected pAkt levels in RL95-2 cells. IGF-II, but not IGF-I, increased pERK1/2 levels in RL95-2-1R-A cells. After AG1024 pretreatment, the proliferation rate and DNA content corresponding to the S phase increased and apoptosis decreased significantly in IGF-II-treated RL95-2-1R-A cells only （P 〈0.05）. Conclusions The proliferation effect of insulin is mediated by IR-A. When IR-A dominates in a cell line, IGF-II activated cell proliferation mainly through the ERKI/2 pathway. On the other hand, IGF-II activated cell proliferation mainly through the Akt pathway. IR-A can at least partly mediate the proliferative and anti-apoptotic effects of IGF-II through the ERKI/2 pathway.展开更多
目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于...目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。展开更多
目的对心律失常行射频消融术患者围手术期发生心脏压塞的危险因素及抢救护理进行范围综述,为完善围手术期管理、改善患者预后提供参考。方法采用Arksey和O`Malley的范围综述方法为框架,检索中国知网、中国生物医学文献数据库、维普中文...目的对心律失常行射频消融术患者围手术期发生心脏压塞的危险因素及抢救护理进行范围综述,为完善围手术期管理、改善患者预后提供参考。方法采用Arksey和O`Malley的范围综述方法为框架,检索中国知网、中国生物医学文献数据库、维普中文科技期刊数据库、万方数据库、Cochrane Library、PubMed、Web of Science、Embase、CINAHL数据库中发表的心律失常患者行射频消融术并发心脏压塞的相关研究,检索时限为建库至2024年1月31日。对纳入文献进行筛选、汇总,并对危险因素进行归纳总结,得出针对危险因素的抢救护理对策。结果最终纳入11篇文献,研究设计以病例对照为主,多数研究纳入射频消融术中及术后发生的心脏压塞,少数研究仅纳入术中心脏压塞。心律失常患者行射频消融术围手术期并发心脏压塞的发生率为0.61%~2.3%,且不同研究中心报告发生率差异较小,影响因素主要包括患者因素、合并疾病及治疗因素、射频消融术操作相关因素、机构相关因素。抢救护理对策有(1)迅速识别,精准处置;(2)人员、设备急救准备;(3)抢救护理技术应用等。结论心律失常患者射频消融术并发心脏压塞受患者、手术操作及组织因素的影响,未来可综合现有研究结果构建心脏压塞风险预测模型,为临床早期识别风险并制订相应的预防策略提供参考。展开更多
文摘AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS: All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% ± 2.4% (mean ± SD), 30.9% ± 5.5%, 23.8% ± 3.9%, 37.1% ± 5.3%, 10.4% ± 4.5%, 52.5% ± 4.5% and 22.6% ± 0.4%, at 2 μmol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% ± 7.6%, 32.9% ± 8.2%, 53.9% ± 8.0%, 52.8% ± 4.0%, 32.3% ± 4.2%, 51.8% ± 4.5%, and 30.6% ± 9.4%, at 50 μmol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% ± 0.2%, 0%, 0%, 2.0% ± 0.1%, 5.0% ± 0.2%, 3.0% ± 0.1%, and 5.0% ± 0.2%, respectively (P < 0.05). LY294002 at 50 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% ± 0.2%, 0%, 3.0% ± 0.2%, 0%, 0%, 0% and 3% ± 0.1%, respectively (P < 0.05). PD980509 at 20 μmol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 μmol/L PPP or 50 μmol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 μmol/L PD98059 did not show apoptosis.CONCLUSION: IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer.
基金This work was supported by grants from the Specialized Research Fund for the Doctoral Program of Higher Education （No. 200800010095） and the National Natural Science Foundation of China （No. 30973181）.
文摘Background Hyperinsulinemia, insulin-like growth factor （IGF）-I and -Ⅱ （IGF-Ⅱ） are associated with increased risk of endometrial carcinoma. Insulin receptor isoform A （IR-A） is more frequently expressed in endombtrial carcinoma than in normal endometrial tissues. To better understand their roles in endometrial carcinoma, we investigated the effects of insulin, IGF-I, and IGF-II in endometrial carcinomas cells with different IR-A expression levels. Methods To explore the role of IR-A in mediating the activity of IGF-I, IGF-II, and insulin, we investigate the cellular proliferation of endometrial carcinoma cell lines RL95-2 and RL95-2-1R-A by MTS assays. Then we examined the protein kinase Akt phosphorylation and extracellular signal-regulated kinase （ERK） 1/2 phosphorylation in both cell lines by Western blotting. The effect of IGF-II and AG1024 on cell cycle progression and apoptosis was assessed by fiowcytometry. To examine whether the effects of IGFs were mediated by IR-A, we blocked IGF-I receptor （IGF-IR） in both cell lines using AG1024, an IGF-IR-specific inhibitor. Results IGF-I and IGF-II significantly enhanced proliferation of both cell lines （P 〈0.05）. By contrast, insulin significantly increased proliferation of RL95-2-1R-A cells only （P 〈0.05）. IGF-I and IGF-II significantly increased pAkt levels in RL95-2 cells and pERK1/2 levels in RL95-2-1R-A cells （all, P 〈0.05）. Insulin increased pERK1/2 levels in RL95-2-1R-A cells only （P 〈0.05）. LY294002 and PD98059 inhibited the specific signaling activities and cellular proliferation. After AG1024 pretreatment, neither IGF-I nor IGF-II affected pAkt levels in RL95-2 cells. IGF-II, but not IGF-I, increased pERK1/2 levels in RL95-2-1R-A cells. After AG1024 pretreatment, the proliferation rate and DNA content corresponding to the S phase increased and apoptosis decreased significantly in IGF-II-treated RL95-2-1R-A cells only （P 〈0.05）. Conclusions The proliferation effect of insulin is mediated by IR-A. When IR-A dominates in a cell line, IGF-II activated cell proliferation mainly through the ERKI/2 pathway. On the other hand, IGF-II activated cell proliferation mainly through the Akt pathway. IR-A can at least partly mediate the proliferative and anti-apoptotic effects of IGF-II through the ERKI/2 pathway.
文摘目的探讨^(131)I治疗对分化型甲状腺癌患者术后血清全段甲状旁腺激素(iPTH)、胰岛素样生长因子1(IGF-1)水平的影响。方法回顾性分析河南科技大学第一附属医院2020年1月至2022年9月收治的73例分化型甲状腺癌患者,均接受甲状腺全切除并于术后2个月采用^(131)I治疗,随访1个月根据治疗情况将患者分为有效组(51例)和无效组(22例)。比较两组患者治疗前及治疗7 d iPTH和IGF-1水平,以及有效组治疗后各时间点血清iPTH、IGF-1水平。结果两组患者治疗后7 d血清iPTH、IGF-1水平均低于治疗前,且有效组低于无效组(P<0.05);有效组治疗后不同时间点血清iPTH、IGF-1水平差异有统计学意义(P<0.05)。结论分化型甲状腺癌患者^(131)I治疗后血清iPTH、IGF-1水平变化可用于判断甲状旁腺功能恢复情况,血清iPTH还可预示术后低钙血症的发生。
文摘目的对心律失常行射频消融术患者围手术期发生心脏压塞的危险因素及抢救护理进行范围综述,为完善围手术期管理、改善患者预后提供参考。方法采用Arksey和O`Malley的范围综述方法为框架,检索中国知网、中国生物医学文献数据库、维普中文科技期刊数据库、万方数据库、Cochrane Library、PubMed、Web of Science、Embase、CINAHL数据库中发表的心律失常患者行射频消融术并发心脏压塞的相关研究,检索时限为建库至2024年1月31日。对纳入文献进行筛选、汇总,并对危险因素进行归纳总结,得出针对危险因素的抢救护理对策。结果最终纳入11篇文献,研究设计以病例对照为主,多数研究纳入射频消融术中及术后发生的心脏压塞,少数研究仅纳入术中心脏压塞。心律失常患者行射频消融术围手术期并发心脏压塞的发生率为0.61%~2.3%,且不同研究中心报告发生率差异较小,影响因素主要包括患者因素、合并疾病及治疗因素、射频消融术操作相关因素、机构相关因素。抢救护理对策有(1)迅速识别,精准处置;(2)人员、设备急救准备;(3)抢救护理技术应用等。结论心律失常患者射频消融术并发心脏压塞受患者、手术操作及组织因素的影响,未来可综合现有研究结果构建心脏压塞风险预测模型,为临床早期识别风险并制订相应的预防策略提供参考。
