On the role of additive hormone monotherapy with tamoxifen,medroxyprogesterone acetate and aminoglutethimide,in advanced breast cancer

Summary We analyzed the results of clinical studies on the therapeutic efficacy of hormone monotherapy with tamoxifen, medroxyprogesterone acetate, and aminoglutethimide in metastatic breast cancer, which were published between 1971 and 1986 and involved altogether 7000 patients. The overall response rates in patients treated with these hormonal single agents at various dose levels ranged from 31%–42%. When only estrogen receptor-positive patients were considered, the response rates lay between 41% and 54% in groups which were treated with the antiestrogenic agents tamoxifen or aminoglutethimide. The duration of remission was 12 months for tamoxifen- and aminoglutethimide-treated women, whereas medroxy-progesterone acetate effected remissions lasting from 6–16 months. The overall mean survival from start of therapy in tamoxifen- and aminoglutethimide-treated groups was 20 months, whereas information concerning this therapeutic parameter was available only in a minority of medroxyprogesterone acetate-treated groups. With respect to the response by site of metastatic lesions, all three agents caused a significantly higher degree of remissions in the soft tissue as compared to visceral disease.Abbreviations AG Aminoglutethimide - MPA Medroxyprogesterone acetate - TAM Tamoxifen     

A combination therapy with mitomycin c, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy for advanced breast cancer refractory to combination chemotherapy of cyclophosphamide, doxorubicin and 5 fluorouracil

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-FU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.     

甲孕酮联合MVP方案与单纯MVP方案治疗晚期非小细胞肺癌的对比研究

目的　观察患者服用甲孕酮合并 MVP方案与单纯使用 MVP方案化疗治疗初治非小细胞肺癌(non- small cell cancer,NSCL C)的疗效 ,生活质量改善 ,毒性等情况并加以比较。方法　 A组 (2 9例 )接受甲孕酮 MVP方案治疗 ,B组 (2 7例 )接受 MVP方案治疗 ,采用单盲随机分组 ,毒性反应按 WHO标准进行评价。结果　 A、B两组疗效 (CR PR)分别为 2 7.6 %及 2 2 .2 % ,P>0 .0 5。中位生存期 A组 30周 ,B组 2 4周 ,(P<0 .0 1)。白细胞、血红蛋白减少及恶心、呕吐反应 ,B组较 A组明显 ,差异有显著性。两组均未发现其他严重的毒性反应。结论　甲孕酮联合 MVP方案组与单纯 MVP方案治疗组疗效差异无显著性 ,但前者中位生存期长 ,患者生活质量改善 ,毒副反应小     

三七血伤宁胶囊联合甲羟孕酮治疗功能失调性子宫出血的疗效观察

目的探讨三七血伤宁胶囊联合醋酸甲羟孕酮片治疗功能失调性子宫出血的临床疗效。方法选取2017年4月—2018年4月在聊城市第二人民医院治疗的功能失调性子宫出血患者86例,根据用药的差别分为对照组(43例)和治疗组(43例)。对照组口服醋酸甲羟孕酮片,4mg/次,2次/d;治疗组在对照组基础上口服三七血伤宁胶囊,0.8g/次,3次/d。两组患者均治疗10 d。观察两组患者临床疗效,同时比较治疗前后两组患者出血控制时间、完全止血时间、血清雌二醇(E2)、卵泡刺激素(FSH)和黄体生成素(LH)水平,以及SAS、SDS和GQOLI-74评分。结果治疗后,对照组临床有效率为81.40%,显著低于治疗组的97.67%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组患者在出血控制时间和完全止血时间均明显早于对照组(P0.05)。治疗后,两组患者E2、FSH、LH水平均显著降低(P0.05),且治疗组明显低于对照组(P0.05)。治疗后,两组患者SAS评分和SDS评分均明显降低(P0.05),而GQOLI-74评分显著升高(P0.05),且治疗组患者这些评分明显好于对照组(P0.05)。结论三七血伤宁胶囊联合醋酸甲羟孕酮片治疗DUB止血效果好,可有效改善性激素水平,改善患者负面情绪,提高患者生活质量。     

尼尔雌醇联合醋酸甲羟孕酮治疗围绝经期妇女类风湿性关节炎的临床观察

目的:观察尼尔雌醇联合醋酸甲羟孕酮治疗围绝经期妇女类风湿性关节炎的临床疗效和安全性。方法:50例围绝经期类风湿性关节炎患者按随机数字表法均分为对照组和观察组。对照组患者给予甲氨蝶呤10 mg,口服,每周1次。观察组患者中未绝经者给予尼尔雌醇1² mg,2周1次+每月月经第23天给予醋酸甲羟孕酮8 mg,连用5 d;绝经者给予尼尔雌醇12 mg,2周1次+每月月经第23天给予醋酸甲羟孕酮8 mg,连用5 d;绝经者给予尼尔雌醇1² mg,2周1次+每32 mg,2周1次+每3⁶个月给予醋酸甲羟孕酮10 mg,连用5 d;子宫已切除者给予尼尔雌醇2 mg,2周1次,症状改善后减至1 mg/2周,或2mg/月+每36个月给予醋酸甲羟孕酮10 mg,连用5 d;子宫已切除者给予尼尔雌醇2 mg,2周1次,症状改善后减至1 mg/2周,或2mg/月+每3⁶个月给予醋酸甲羟孕酮10 mg/d,连用5 d。两组患者均适当补充钙剂和维生素D。两组患者均治疗6个月后观察临床疗效,并观察治疗前后体征和实验室指标,雌二醇、胫骨骨密度水平及不良反应发生情况。结果:观察组患者总有效率显著低于对照组,差异有统计学意义(P<0.05);两组患者治疗前体征、实验室指标和雌二醇、胫骨骨密度水平比较,差异无统计学意义(P>0.05);两组患者治疗后体征、实验室指标均显著低于同组治疗前,但观察组显著高于对照组,差异均有统计学意义(P<0.05);对照组患者雌二醇、胫骨骨密度水平治疗后与治疗前比较,差异均无统计学意义(P>0.05),而观察组治疗后与治疗前比较差异有统计学意义(P<0.05)。观察组患者不良反应发生率显著低于对照组,差异有统计学意义(P<0.05)。结论:尼尔雌醇联合醋酸甲羟孕酮尽管总有效率低于甲氨蝶呤,但仍能显著改善临床症状,且在增加雌激素和骨密度水平及安全性方面优于甲氨蝶呤。     

甲孕酮合并化疗改善晚期肺癌患者生活质量的临床观察

目的　观察患者服用甲孕酮后改善化疗所致的厌食、体重下降、ECOG下降、骨髓抑制及胃肠道反应的作用及止痛和促进蛋白同化作用。方法　 130例接受化疗的晚期肺癌患者 ,分成单用化疗组及化疗 甲孕酮组。结果　在化疗 甲孕酮组治疗的 160个周期中有 4 3.1%食量增加 ;4 5%体重增长 ,平均每周期体重增加 0 .74± 1.56kg;血浆白蛋白升高 1.2± 2 .9g/ L、88.1%疼痛减轻及 2 8.1% ECOG改善。化疗的毒副作用 ,出现 度以上的白细胞下降占 33.8%、血红蛋白下降占 15.6%及胃肠道反应占 18.1%。结论　甲孕酮如能正确合理地用于晚期癌症的治疗 ,可以全面改善化疗期癌症患者的生活质量。     

Effect of long-term progestin treatment on endometrial vasculature in normal cycling mice

The aim of this study was to develop a mouse model to investigate the effects of long-term progestin-only exposure on endometrial vascular structure. Normal cycling mice received Silastic implants containing either medroxyprogesterone acetate (MPA) or levonorgestrel (LNG) and were dissected after 1, 3 or 6 weeks. Endometrial vascular density increased significantly within 1 week of MPA (482 +/- 40.2 vessels/mm2) or LNG (440 +/- 26.5 vessels/mm2) treatment compared with normal cycling mice (293 +/- 10.5 vessels/mm2). MPA increased stromal cell density within 1 week of treatment (13813 +/- 1450 cells/mm2) compared with normal cycling mice (8256 +/- 928 cells/mm2). However, although LNG significantly increased stromal cell density overall, the increase did not reach significance within the individual weeks examined. There was no significant change in the ratio of vascular to stromal cell density among treated and normal cycling mice. Epithelial cell height significantly decreased within 1 week of LNG (17.6 +/- 1.3 microm) treatment compared with normal cycling mice (23.5 +/- 1.3 microm); epithelial cell height also decreased within 1 week of MPA treatment (16.6 +/- 2.1 microm), although this did not reach statistical significance. VEGF immunostaining increased significantly in luminal epithelium after MPA or LNG treatment, and in glandular epithelium after LNG treatment. These observations are similar to those reported in human endometrium, suggesting that this mouse model may facilitate further investigations into breakthrough bleeding due to long-term progestin use.     

大剂量米非司酮和孕激素联合应用治疗子宫内膜癌的临床研究

目的　研究大剂量米非司酮、大剂量孕激素以及二者联合应用对子宫内膜癌患者的治疗效果 ,并探讨其作用机制。方法　将 3 0例经诊刮确诊的子宫内膜癌患者随机分为 3组 ,每组 10例 ,术前用药 5d。米非司酮组术前用米非司酮 ( 10 0mg d) ,醋酸甲羟孕酮组术前用醋酸甲羟孕酮 ( 50 0mg d) ,联合组术前用米非司酮 ( 10 0mg d)、醋酸甲羟孕酮 ( 50 0mg d)。各组用药前后行自身对照 ,观察癌细胞组织形态学改变及雌激素受体 (ER)、孕激素受体 (PR)、增殖细胞核抗原 (PCNA)、凋亡相关基因 (bcl 2、bax)及CD44 v6基因表达的变化。结果　各组治疗后 ,癌细胞分化均趋向成熟 ,分泌活跃 ,可在癌组织中观察到凋亡的癌细胞 ,联合组治疗后变化最明显。醋酸甲羟孕酮组治疗前后 ,免疫组织化学 (免疫组化 )评分分别为PR( 2 9± 1 1、1 6± 0 8)、ER( 2 8± 0 9、1 4± 0 9)、PCNA( 0 84± 0 11、0 60±0 12 )、bcl 2 ( 0 2 3 6± 0 0 89、0 157± 0 981)和CD44 v6( 4 6± 1 8、2 5± 1 9) ,表达均降低 (所有P <0 0 1) ,bax( 0 2 0± 0 10、0 42± 0 0 7)表达增多 (P <0 0 1)。米非司酮组治疗前后免疫组化评分分别为PR( 3 4± 1 0、1 9± 0 8)、ER( 2 7± 0 9、1 2± 0 7)、PCNA( 0 80± 0 15、0     

醋酸甲羟孕酮增强顺铂对人卵巢癌耐药细胞抗癌作用的研究

目的:观察醋酸甲羟孕酮(MPA)对人卵巢癌CoC1/cDDP细胞移植瘤的生长抑制作用及对DDP的耐药逆转作用,并分析其作用机制。方法:建立人卵巢癌裸鼠皮下移植瘤模型,随机分为4组,每组5只。(1)对照组:腹腔注射等体积生理盐水;(2)DDP治疗组:每只每次腹腔注射DDP 3mg/kg。(3)MPA治疗组:每只每次灌胃30mg/kg;(4)联合治疗组:每只每次灌胃MPA 30mg/kg,1h后每只每次腹腔注射DDP 3mg/kg,每隔2天给药1次,共4次,于治疗第1、5、10、15、20天分别测瘤体积,20天后处死裸鼠,完整剥出瘤组织,称瘤重,计算抑瘤率;通过流式细胞仪检测亚G1期细胞及AnnexinV+/PI-细胞鉴定细胞凋亡,分析移植瘤细胞周期;用半定量RT-PCR法检测移植细胞组织Survivin-ΔEx3、caspase-3、P21WAF1/CIP1及GST-π4基因mRNA表达。结果:(1)MPA组、MPA+DDP组治疗第10天起皮下移植瘤体积明显小于DDP组和对照组,且进行性缩小(P<0.01);抑瘤率分别为51.63%、62.21%,均明显大于DDP组的6.84%(P<0.01),并且两组间有显著差异(P<0.01);(2)流式细胞仪分析显示,移植瘤出现亚G1期峰及AnnexinV+/PI-细胞均证实MPA能诱导CoC1/cDDP细胞凋亡,并显著高于对照组及DDP组,并出现G1期阻滞;与DDP合用除出现G1期阻滞外又出现G2/M期阻滞,S期明显减少,亚G1期细胞及AnnexinV+/PI-细胞进一步上升;(3)半定量RT-PCR检测显示,MPA组Survivin-ΔEx3、GST-πmRNA下调,而P21WAF1/CIP1、caspase-3 mRNA上调,与DDP合用后,对Survivin-ΔEx3、P21WAF1/CIP1及GST-πmRNA的表达无协调作用,而对caspase-3 mRNA有协同上调作用。结论:MPA通过阻滞G0/G1期明显抑制了CoC1/cDDP移植瘤生长,并有很强的致凋亡作用,同时下调GST-πmRNA,从而逆转对顺铂耐药。