Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. Ho...Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. However, within 2 years 65% of these patients relapse and thereafter only receive palliative care. Novel therapies based on the biology of these cancers are urgently needed. The opioid growth factor (OGF)-OGF receptor (OGFr) axis is an endogenous opioid system known to inhibit proliferation of human ovarian cancer cells in tissue culture, but does not affect cell survival. The present study determined whether OGF in combination with standard of care chemotherapy, provides an inhibitory effect on the growth of human ovarian cancer cells in vitro. In addition, this investigation assessed whether OGF biotherapy, alone or in combination with taxol or cisplatin, inhibits tumor growth in mice with xenografts of ovarian cancer. The combination of OGF (10–6 M) with taxol (10–9 M or 10–10 M) or cisplatin (0.01 ug/ml or 0.001 ug/ml) markedly reduced cell number and DNA synthesis in vitro to a greater extent than individual compounds. OGF, but not taxol or cisplatin, altered growth in an opioid receptor mediated and reversible manner. Female nu/nu mice inoculated subcutaneously with SKOV-3 cells, and treated with OGF (10 mg/kg) for 5 weeks commencing at the time tumors became measurable, had tumor volumes and weight that were reduced by up to 50% from animals receiving saline. The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. Moreover, OGF treatment in mice receiving cisplatin provided protection against the weight loss associated with cisplatin alone. All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. Additive inhibitory effects on DNA synthesis and angiogenesis were recorded in animals treated with both OGF and taxol, or OGF and cisplatin, in comparison to individual compounds alone. OGF and OGFr were detected in tumor tissue;however OGFr expression was reduced 51% - 81% by OGF treatment. This preclinical evidence demonstrates that OGF biotherapy markedly inhibits ovarian tumorigenesis in a non-toxic manner, and can be combined with taxol or cisplatin to provide an enhanced therapeutic benefit.展开更多
目的探讨艾司氯胺酮无阿片全身麻醉对老年全髋关节置换术(THR)患者神经源炎性因子、脑氧代谢、麻醉及苏醒质量的影响。方法选取2022年4月—2023年4月择期行THR的老年患者86例,随机将其分为观察组和对照组2组各43例。观察组行艾司氯胺酮...目的探讨艾司氯胺酮无阿片全身麻醉对老年全髋关节置换术(THR)患者神经源炎性因子、脑氧代谢、麻醉及苏醒质量的影响。方法选取2022年4月—2023年4月择期行THR的老年患者86例,随机将其分为观察组和对照组2组各43例。观察组行艾司氯胺酮无阿片麻醉,对照组行常规麻醉。比较2组麻醉诱导前、气管插管时(T2)、切皮时(T3)、拔出气管导管时(T4)血流动力学[平均动脉压(MAP)和心率(HR)]、神经源炎性因子[神经生长因子(NGF)、前列腺素E_(2)(PGE_(2))、P物质和神经激肽A(NKA)]、脑保护作用指标[脑氧摄取率(CERO_(2))、动脉-颈内静脉球部血氧差(Da-jvO_(2))、神经元特异性烯醇化酶(NSE)和S-100β蛋白],术后第1、2、3天疼痛视觉模拟评分法(VAS)、术后恶心呕吐(PONV)评分,术前和术后第1、3、7天简明精神状态量表(MMSE)评分,苏醒质量,以及术中、术后不良反应。结果T2~T4时,2组MAP和HR均呈现升高趋势,NGF、PGE_(2)、SP、NKA、CERO_(2)、Da-jvO_(2)、NSE和S-100β蛋白均呈现降低趋势;且观察组MAP和HR均高于对照组,NGF、PGE_(2)、SP、NKA、CERO_(2)、Da-jvO_(2)、NSE和S-100β蛋白均低于对照组(P<0.05)。术后第1、2及3天,2组VAS和PONV评分均呈下降趋势,术后第1、3及7天MMSE评分均呈升高趋势;且观察组术后第1、2及3天VAS和PONV评分低于对照组,术后第1、3及7天MMSE评分高于对照组(P<0.05)。观察组拔管时间和苏醒时间均短于对照组,拔管后10 min Ramsay评分低于对照组(P<0.05)。术中和术后,观察组不良反应发生率为11.63%(5/43)低于对照组37.21%(16/43)(P<0.05)。结论艾司氯胺酮无阿片全身麻醉用于老年THR患者有利于稳定血流动力学,提高术后苏醒质量,缓解疼痛感,且能改善脑氧代谢,降低不良反应发生率,分析可能与其调节神经源炎症反应有关。展开更多
目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-N...目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-NC组、si-OGFRP1组、miR-NC组、miR-665组、si-OGFRP1+anti-miR-NC组、si-OGFRP1+anti-miR-665组。四甲基偶氮唑盐比色法(MTT)检测细胞存活率;Transwell检测细胞迁移和侵袭;双荧光素酶报告实验检测OGFRP1和miR-665的靶向关系。结果与正常卵巢组织相比,卵巢癌组织中OGFRP1表达水平升高(2.75±0.27 vs 1.00±0.09),miR-665表达水平降低(0.51±0.05 vs 1.00±0.08)(均P<0.05)。抑制OGFRP1表达或过表达miR-665后,卵巢癌A2780细胞的活性、细胞迁移与侵袭数均降低(均P<0.05)。双荧光素酶报告实验结果显示,OGFRP1靶向调控miR-665;抑制miR-665和OGFRP1表达后,卵巢癌A2780细胞活性升高,迁移、侵袭细胞数增加(P<0.05)。结论抑制OGFRP1表达可抑制卵巢癌A2780细胞增殖、迁移和侵袭,其机制可能与上调miR-665有关。展开更多
文摘Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. However, within 2 years 65% of these patients relapse and thereafter only receive palliative care. Novel therapies based on the biology of these cancers are urgently needed. The opioid growth factor (OGF)-OGF receptor (OGFr) axis is an endogenous opioid system known to inhibit proliferation of human ovarian cancer cells in tissue culture, but does not affect cell survival. The present study determined whether OGF in combination with standard of care chemotherapy, provides an inhibitory effect on the growth of human ovarian cancer cells in vitro. In addition, this investigation assessed whether OGF biotherapy, alone or in combination with taxol or cisplatin, inhibits tumor growth in mice with xenografts of ovarian cancer. The combination of OGF (10–6 M) with taxol (10–9 M or 10–10 M) or cisplatin (0.01 ug/ml or 0.001 ug/ml) markedly reduced cell number and DNA synthesis in vitro to a greater extent than individual compounds. OGF, but not taxol or cisplatin, altered growth in an opioid receptor mediated and reversible manner. Female nu/nu mice inoculated subcutaneously with SKOV-3 cells, and treated with OGF (10 mg/kg) for 5 weeks commencing at the time tumors became measurable, had tumor volumes and weight that were reduced by up to 50% from animals receiving saline. The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. Moreover, OGF treatment in mice receiving cisplatin provided protection against the weight loss associated with cisplatin alone. All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. Additive inhibitory effects on DNA synthesis and angiogenesis were recorded in animals treated with both OGF and taxol, or OGF and cisplatin, in comparison to individual compounds alone. OGF and OGFr were detected in tumor tissue;however OGFr expression was reduced 51% - 81% by OGF treatment. This preclinical evidence demonstrates that OGF biotherapy markedly inhibits ovarian tumorigenesis in a non-toxic manner, and can be combined with taxol or cisplatin to provide an enhanced therapeutic benefit.
文摘目的探讨艾司氯胺酮无阿片全身麻醉对老年全髋关节置换术(THR)患者神经源炎性因子、脑氧代谢、麻醉及苏醒质量的影响。方法选取2022年4月—2023年4月择期行THR的老年患者86例,随机将其分为观察组和对照组2组各43例。观察组行艾司氯胺酮无阿片麻醉,对照组行常规麻醉。比较2组麻醉诱导前、气管插管时(T2)、切皮时(T3)、拔出气管导管时(T4)血流动力学[平均动脉压(MAP)和心率(HR)]、神经源炎性因子[神经生长因子(NGF)、前列腺素E_(2)(PGE_(2))、P物质和神经激肽A(NKA)]、脑保护作用指标[脑氧摄取率(CERO_(2))、动脉-颈内静脉球部血氧差(Da-jvO_(2))、神经元特异性烯醇化酶(NSE)和S-100β蛋白],术后第1、2、3天疼痛视觉模拟评分法(VAS)、术后恶心呕吐(PONV)评分,术前和术后第1、3、7天简明精神状态量表(MMSE)评分,苏醒质量,以及术中、术后不良反应。结果T2~T4时,2组MAP和HR均呈现升高趋势,NGF、PGE_(2)、SP、NKA、CERO_(2)、Da-jvO_(2)、NSE和S-100β蛋白均呈现降低趋势;且观察组MAP和HR均高于对照组,NGF、PGE_(2)、SP、NKA、CERO_(2)、Da-jvO_(2)、NSE和S-100β蛋白均低于对照组(P<0.05)。术后第1、2及3天,2组VAS和PONV评分均呈下降趋势,术后第1、3及7天MMSE评分均呈升高趋势;且观察组术后第1、2及3天VAS和PONV评分低于对照组,术后第1、3及7天MMSE评分高于对照组(P<0.05)。观察组拔管时间和苏醒时间均短于对照组,拔管后10 min Ramsay评分低于对照组(P<0.05)。术中和术后,观察组不良反应发生率为11.63%(5/43)低于对照组37.21%(16/43)(P<0.05)。结论艾司氯胺酮无阿片全身麻醉用于老年THR患者有利于稳定血流动力学,提高术后苏醒质量,缓解疼痛感,且能改善脑氧代谢,降低不良反应发生率,分析可能与其调节神经源炎症反应有关。
文摘目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-NC组、si-OGFRP1组、miR-NC组、miR-665组、si-OGFRP1+anti-miR-NC组、si-OGFRP1+anti-miR-665组。四甲基偶氮唑盐比色法(MTT)检测细胞存活率;Transwell检测细胞迁移和侵袭;双荧光素酶报告实验检测OGFRP1和miR-665的靶向关系。结果与正常卵巢组织相比,卵巢癌组织中OGFRP1表达水平升高(2.75±0.27 vs 1.00±0.09),miR-665表达水平降低(0.51±0.05 vs 1.00±0.08)(均P<0.05)。抑制OGFRP1表达或过表达miR-665后,卵巢癌A2780细胞的活性、细胞迁移与侵袭数均降低(均P<0.05)。双荧光素酶报告实验结果显示,OGFRP1靶向调控miR-665;抑制miR-665和OGFRP1表达后,卵巢癌A2780细胞活性升高,迁移、侵袭细胞数增加(P<0.05)。结论抑制OGFRP1表达可抑制卵巢癌A2780细胞增殖、迁移和侵袭,其机制可能与上调miR-665有关。
