放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

子宫输卵管造影心理护理及并发症处理

子宫输卵管造影术（H．S．G）是妇产科检查子宫及输卵管疾病的常用方法之一。目前主要用于诊断原发及继发不孕。本文主要探讨配合子宫输卵管造影术的心理护理及并发症的处理。1资料与方法我们复习了从1994～1997年6月所做的H．S．G300例。年龄22～40岁，平均28岁。主诉不孕。患者常规准备，在妇科插管后，X线直视下由妇科医师注药，放射科医师透视下观察并适时摄片。造影剂配制：泛影葡胺20ml，庆大霉素4万U，地塞米松2ml，糜蛋白酶4000U。2结果正常131例，子宫畸形5例，输卵管不通104例，伴积液65例。并发症：一般轻者有下腹不适，恶心…     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

顺铂和洛铂与放射联合对小鼠肺癌移植瘤生长的影响

目的 了解顺铂、洛铂给药后不同时间照射对小鼠肺癌移植瘤的放射增敏作用影响.方法 70只C57BL/6近交系Lewis肺癌移植小鼠随机分组,按10 mg药物/kg体重经尾静脉分别注射顺铂和洛铂,给药后在0.5、2.0、4.0、24.0、48.0、72.0、96.0 h分别将小鼠处死获取肿瘤组织标本,应用ICP-MS方法测定标本铂含量.80只荷瘤小鼠随机分为对照、单纯药物、单纯照射、药物联合照射组共10个组,注射药物后1、24 h或72 h对肿瘤局部进行照射,比较各组间肿瘤大小.结果 顺铂、洛铂在肿瘤组织浓度均在给药后迅速达到4.78、2.79 μg/g (t=3.82,P=0.005),4 h后分别降至3.39、0.99 μg/g (t=9.10,P=0.000),96 h时分别为1.41、0.23 μg/g (t=3.70,P=0.006).顺铂给药后1、24、72 h照射组之间肿瘤生长速度相似,但比对照组、单纯照射组、单纯顺铂组均明显变缓;在第15天时肿瘤相对体积分别为4.73、5.52、2.15(F=0.84,P=0.451),而对照组、单纯照射组、单纯顺铂组分别为16.63(F=10.50,P=0.000)、10.34(F=3.12,P=0.046)、12.80(F=8.06,P=0.001).洛铂给药后1、24、72 h照射组之间肿瘤生长速度也相似,但与对照组、单纯照射组、单纯洛铂组相比均明显变缓;在第15天时肿瘤相对体积分别为3.49、4.90、3.86(F=0.32,P=0.727),而对照组、单纯照射组、单纯洛铂组分别为16.63(F=15.21,P=0.000)、10.34(F=4.12,P=0.016)、14.28(F=10.67,P=0.000).顺铂和洛铂在1、24、72 h的放射增敏比分别为2.13、2.03、3.45和2.53、2.00、2.50.结论 顺铂一次给药后肿瘤内药物浓度至少能持续96 h,其放射增敏作用能持续较长时间;洛铂具有与顺铂相似的抗肿瘤效果及放射增敏作用.

Abstract：

Objective To learn the effect of different combination model between irradiation and cisplatin or lobaplatin on the radiosensitization of xenographt tumor in mice.Methods Seventy C57BL/6 mice with Lewis lung carcinoma were randomly divided into fourteen groups.Then a single intravenous bolus injection of 10 mg/kg either cisplatin or lobaplatin was given.Tumor tissues were collected at the indicated times of 0.5 h, 2.0 h, 4.0 h, 24.0 h, 48.0 h, 72.0 h, and 96.0 h.The platinum levels were determined by inductively coupled plasma-mass spectrometry.Eighty tumor-bearing mice were randomly divided into 10 groups, including a blank control group, a irradiation group, two drug treatment groups and 6 combined treatment groups.The tumors were irradiated at 1 h, 24 h or 72 h after either cisplatin or lobaplatin injection.The tumor size of the groups was compared.Results The concentrations of cisplatin and lobaplatin in tumors rapidly reached 4.78 μg/g and 2.79 μg/g (t=3.82,P=0.005), respectively, then declined rapidly to 3.39 μg/g and 0.99 μg/g (t=9.10,P=0.000) at 4 h, 1.41 μg/g and 0.23 μg/g (t=3.70,P=0.006) at 96 h, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after cisplatin was similar, which was slower than the blank control group, the irradiation group and the cisplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 4.73, 5.52 and 2.15(F=0.84,P=0.451), While was 16.63(F=10.50,P=0.000) in the blank control group, 10.34(F=3.12,P=0.046) in the irradiation group, and 12.80(F=8.06,P=0.001) in the cisplatin treatment group, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after lobaplatin was also similar, which was slower than the blank control group, the irradiation group and the lobaplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 3.49, 4.90 and 3.86(F=0.32,P=0.727), While was 16.63(F=15.21,P=0.000) in the blank control group, 10.34(F=4.12,P=0.016) in the irradiation group, and 14.28(F=10.67,P=0.000) in the lobaplatin treatment group, respectively.The sensitizing enhancement ratio (SER) at 1 h, 24 h and 72 h after the injection were 2.13, 2.03 and 3.45 of cisplatin, and 2.53, 2.00 and 2.50 of lobaplatin, respectively.Conclusions After intravenous bolus injection, the cisplatin concentration in the tumor can be kept at least 96 hours, which results in a persistent radiosensitizing effect.Lobaplatin and cisplatin have similar anti-tumor and radiosensitizing effect.     

荷瘤小鼠静脉注射洛铂和顺铂后药物浓度的变化规律

目的研究洛铂和顺铂在小鼠血浆、肾脏和肿瘤内的药物浓度随时间变化的规律,为放疗增敏提供实验数据。方法 70只C57BL/6近交系Lewis肺癌荷瘤小鼠随机分组,按10mg药物/kg体重经尾静脉分别给小鼠注射药物（洛铂或顺铂）,给药后在0.5、2、4、24、48、72、96 h分别将小鼠处死获取血液和组织标本（肿瘤和肾脏）,应用ICP-MS方法测定标本铂含量。结果洛铂和顺铂的血浆药时曲线均符合三室模型,半衰期分别为51.139h和35.583h,洛铂在血浆中的清除速率大于顺铂[0.532L/（h.kg）对0.192 L/（h·kg）];洛铂和顺铂在肿瘤组织的浓度均在给药后迅速达到最大[（2.79±0.35）μg/g对（4.78±1.11）μg/g],然后迅速下降,在4 h后分别降至0.99±0.21μg/g和3.39±0.55μg/g,在96 h肿瘤中仍有药物存在,浓度分别为0.23±0.05μg/g和1.41±0.71μg/g。肿瘤药物浓度与血浆药物浓度呈对数相关,Rsq分别为0.948和0.837。结论洛铂和顺铂在小鼠体内静脉给药后半衰期长,肿瘤内药物浓度在给药后很快达到最大,在4 h降至平台期,96 h仍有药物存在,顺铂在肿瘤内的浓度高于洛铂;洛铂在小鼠体内的清除速率快于顺铂;可以通过检测血浆中的洛铂和顺铂浓度来估算肿瘤内的药物浓度。     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

石家庄市乳腺癌的筛查结果分析

目的 分析石家庄市部分社区居民乳腺癌的检出率,加强乳腺癌的二级预防,明确早诊、早治的意义.方法 选取2019年1月至2020年1月石家庄市区3个社区居民≥40岁女性进行筛查,采用乳腺癌危险因素评估问卷筛出高危人群,40～44岁高危女性先行乳腺超声检查,BI-RADSⅢ级以上(可疑阳性)者再行钼靶检查.>44岁者采用彩超联合钼靶检查,以BI-RADSⅣ级和Ⅴ级作为阳性结果.分析调查人群基本情况;调查人群乳腺癌筛查结果;比较高危人群特征与临床筛查结果;临床乳腺癌阳性筛查的多因素分析.结果 参加问卷调查的3213人中1105例(34.39％)被筛查为高危,实际参加进一步临床检查有975例(30.35％).其中932例行超声检查,BI-RADS 4A级31例(3.30％),BI-RADS 4B级8例(0.86％),BI-RADS 4C级3例(0.03％),BI-RADS 5级0例.钼靶检查798例,BI-RADS 4A级24例(3.00％),BI-RADS 4B级5例(0.06％),BI-RADS 4C级2例(0.02％),BI-RADS 5级0例.乳腺超声和钼靶均检查751例,两项检查均为阳性26例(3.50％),均为BI-RADS 4A级17例(2.30％),均为BI-RADS 4B级3例(0.40％),均为BI-RADS 4C级2例(0.30％),均为BI-RADS 5级0例.各阳性人员均推荐进一步检查,其中10例进行乳腺肿块活检,1例(0.01％)患者确诊为乳腺癌.经多因素分析,年龄40～59岁、饮酒习惯、精神压抑、乳腺癌家族史是影响临床乳腺癌阳性筛查结果的独立危险因素.结论 石家庄市乳腺癌检出率较高,应广泛展开乳腺癌筛查工作,做到早预防、早诊治,以改善乳腺癌预后.     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

目的 观察放射线联合p53基因及内皮抑素治疗C57BL/6小鼠前列腺癌皮下移植瘤的效果,并初步探讨其作用机制。方法 建立C57BL/6小鼠前列腺癌皮下移植瘤模型。随机分成5组:空白组(A)、放射组(B)、放射线联合p53基因组(C)、放射线联合内皮抑素组(D)及放射线联合p53基因和内皮抑素组(E)。第1天C、E组瘤内注射p53基因腺病毒(1×1vp),第1~14天D、E组每日1次腹腔注射内皮抑素(1.5mg/kg)。第4天B、C、D、E组小鼠肿瘤区单次照射(6 MV X线D_T 15Gy)。每日测量肿瘤体积;检测各组肿瘤标本P53、Ki67及血管内皮生长因子(VEGF)的表达及微血管密度值(MVD)。结果 4个治疗组的肿瘤生长速度均低于空白组(P=0.000),其中E组生长最慢(P<0.05)。免疫组织化学结果:4个治疗组P53的表达均明显低于空白组(P=0.000);4个治疗组Ki67的表达均高于空白组,但变化趋势不同:B、C组Ki67的表达值接近,均随时间的推移而逐渐升高(P=0.000),D、E组的表达则呈现波动性;第5天时E组VEGF的表达最低(P<0.05);肿瘤生长过程中各组MVD值均持续升高,C、D、E 3组MVD值在各时间均高于空白组(P<0.05)。结论 放射线联合p53基因及内皮抑素的抑瘤效果优于单独放射治疗及放射线联合p53基因或内皮抑素。三者均有自己的作用机制,但相互之间可以互相影响。