维甲酸联合诱导治疗骨髓增生异常综合征──骨髓组织病理与涂片初步研究

本文报告应用维甲酸等药物联合诱导治疗骨髓增生异常综合征１０例的骨髓组织病理与涂片的观察结果。治疗后，在骨髓组织病理检查中发现所有患者的病态造血功能可有不同程度改善。从而认为对骨髓异常综合征的治疗效果的评价骨髓组织病理比涂片更佳。

维甲酸等联合诱导治疗难治性贫血18例分析

本文总结了１８例难治性贫血患者应用全反式维甲酸，１，２５（ＯＨ）２维生素Ｄ３和干扰素或小剂量Ａｒａ－ｃ或小剂量三尖杉治疗，完全缓解２例，明显进步３例，进步６例，总有效率６１．１１％。生效时间中位数４０．５天，达标时间中位数５５天。副作用患者均可耐受，该联合诱导方案弥补了单一用药疗效差的缺陷。

恶性肿瘤联合诱导分化治疗的研究现状

肿瘤诱导分化是指应用某些化学物质可使不成熟的恶性细胞逆转,向正常分化,去分化的肿瘤细胞也可被诱导而重新向正常细胞分化,甚至转变成正常细胞。这些化学物质就称为肿瘤诱导分化剂。目前常用的肿瘤诱导分化剂包括维甲酸(RA)类、组蛋白酶抑制剂、甲基化抑制剂、PPAR激动剂、羟甲基戊二酰辅酶A还原酶抑制剂等。近年来探索性用于诱导多种恶性肿瘤,如甲状腺癌、乳腺癌、前列腺癌,其诱导机制是上调NISmRNA的表达,提高肿瘤细胞的碘摄取率。单独利用不同诱导分化剂在基因转录前后的不同环节发挥作用诱导肿瘤的分化或再分化,诱导机制逐渐明确,大多数在体外研究中对培养的各种肿瘤细胞诱导效果较确切,而体内实验疗效不佳,且副作用大。目前研究中多用RA类联合其他类型诱导分化剂,恶性肿瘤种类多局限为甲状腺癌、乳腺癌、前列腺癌等,诱导机制可能为多种诱导分化剂间通过受体相互作用或联合应用诱导NISmRNA表达增加和诱导NIS蛋白定位正确的药物等。探讨低剂量多药联合应用,为肿瘤治疗提供了新的思路,是肿瘤诱导分化治疗的一个十分重要的发展方向。从体外到体内,从基础研究到临床应用,还需要更广泛的探索,应加强诱导分化机制的研究,以求获得突破性进展。

光动力联合细胞疗法治疗中晚期食管癌的临床疗效

目的:探讨光动力联合细胞疗法治疗中晚期食管癌的临床疗效及免疫效应。方法:收治中晚期食管癌患者90例,采用非随机对照的方法,按治疗意愿分为3组:A组30例,仅行单纯光动力治疗;B组30例,行光动力联合CIK治疗;C组30例,仅行单纯CIK治疗。对所有患者进行评估疗效,监测生活质量、免疫功能,随访6个月、1年死亡人数。结果:B组、A组临床总有效率均高于C组(90.0%vs.86.7%vs.63.3%,P<0.05),B组与A组疗效相当(P>0.05);B组生存质量提高率均显著高于A组、C组(86.7%vs.60.0%vs.33.3%,P<0.05),A组高于C组(60.0%vs.33.3%,P<0.05);B组CD3+、CD3+CD56+较A组、C组有明显改善(P<0.05),A组与C组比较差异无统计学意义;3组6个月生存率比较差异无统计学意义,B组1年生存率高于A组、C组(73.9%vs.55.6%vs.29.4%,P<0.05)。结论 :光动力联合细胞疗法具有免疫协同作用,能提高患者机体整体免疫功能,明显改善患者生存质量,延长生存期,显示了良好的临床前景。

Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats

AIM:To investigate the effects of hexahydrocurcumin(HHC),and its combination with 5-fluorouracil(5-FU) on dimethylhydrazine(DMH)-induced colon cancer in rats.METHODS:Male Wistar rats weighing 100-120 g were used as subject models.Aberrant crypt foci(ACF),early preneoplastic lesions of colon cancer,were induced by subcutaneous injection of DHM(40 mg/kg) twice a week for two weeks.After the first DMH injection,rats were treated daily with vehicle(n = 12),curcumin(CUR)(50 mg/kg)(n = 12),HHC(50 mg/kg) orally(n = 12),and treated weekly with an intraperitoneal injection of 5-FU(50 mg/kg)(n = 12),or a combination of 5-FU plus CUR(n = 12) and HHC(n = 12) at the same dosage(s) for 16 wk.The total number of ACF and large ACF were assessed.Cyclooxygenase(COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues.The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted.Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method.Apoptotic index(AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS:The total number of ACF was highest in the DMH-vehicle group(1558.20 ± 17.37),however,the number of ACF was significantly reduced by all treatments,5-FU(1231.20 ± 25.62 vs 1558.20 ± 17.37,P < 0.001),CUR(1284.20 ± 25.47 vs 1558.20 ± 17.37,P < 0.001),HHC(1086.80 ± 53.47 vs 1558.20 ± 17.37,P < 0.001),DMH-5-FU + CUR(880.20 ± 13.67 vs 1558.20 ± 17.37,P < 0.001) and DMH-5-FU + HHC(665.80 ± 16.64 vs 1558.20 ± 17.37,P < 0.001).Interestingly,the total number of ACF in the combined treatment groups,the DMH-5-FU + CUR group(880.20 ± 13.67 vs 1231.20 ± 25.62,P < 0.001;880.20 ± 13.67 vs 1284.20 ± 25.47,P < 0.001) and the DMH-5-FU + HHC group(665.80 ± 16.64 vs 1231.20 ± 25.62,P < 0.001;665.80 ± 16.64 vs 1086.80 ± 53.47,P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone.Large ACF were also significantly reduced in all treatment groups,5-FU(111.00 ± 7.88 vs 262.20 ± 10.18,P < 0.001),CUR(178.00 ± 7.33 vs 262.20 ± 10.18,P < 0.001),HHC(186.60 ± 21.51 vs 262.20 ± 10.18,P < 0.001),DMH-5-FU + CUR(122.00 ± 5.94 vs 262.20 ± 10.18,P < 0.001) and DMH-5-FU + HHC(119.00 ± 17.92 vs 262.20 ± 10.18,P < 0.001) when compared to the vehicle group.Furthermore,in the DMH-5-FU + CUR and DMH-5-FU + HHC groups the formation of large ACF was significantly reduced when compared to CUR(122.00 ± 5.94 vs 178.00 ± 7.33,P < 0.005) or HHC treatment alone(119.00 ± 17.92 vs 186.60 ± 21.51,P < 0.001),however,this reduction was not statistically different to 5-FU monotherapy(122.00 ± 5.94 vs 111.00 ± 7.88,P = 0.217;119.00 ± 17.92 vs 111.00 ± 7.88,P = 0.619,respectively).The levels of COX-1 protein after all treatments were not different from normal rats.A marked increase in the expression of COX-2 protein was observed in the DMH-vehicle group.Over-expression of COX-2 was not significantly decreased by 5-FU treatment alone(95.79 ± 1.60 vs 100 ± 0.00,P = 0.198).However,over-expression of COX-2 was significantly suppressed by CUR(77.52 ± 1.68 vs 100 ± 0.00,P < 0.001),HHC(71.33 ± 3.01 vs 100 ± 0.00,P < 0.001),5-FU + CUR(76.25 ± 3.32 vs 100 ± 0.00,P < 0.001) and 5-FU + HHC(68.48 ± 2.24 vs 100 ± 0.00,P < 0.001) in the treated groups compared to the vehicle group.Moreover,CUR(77.52 ± 1.68 vs 95.79 ± 1.60,P < 0.001),HHC(71.33 ± 3.01 vs 95.79 ± 1.60,P < 0.001),5-FU + CUR treatments(76.25 ± 3.32 vs 95.79 ± 1.60,P < 0.001) and 5-FU + HHC(68.48 ± 2.24 vs 95.79 ± 1.60,P < 0.001) markedly decreased COX-2 protein expression more than 5-FU alone.Furthermore,the AI in all treated groups,5-FU(38.86 ± 4.73 vs 23.56 ± 2.12,P = 0.038),CUR(41.78 ± 6.92 vs 23.56 ± 2.12,P < 0.001),HHC(41.06 ± 4.81 vs 23.56 ± 2.12,P < 0.001),5-FU + CUR(49.05 ± 6.75 vs 23.56 ± 2.12,P < 0.001) and 5-FU + HHC(53.69 ± 8.59 vs 23.56 ± 2.12,P < 0.001) significantly increased when compared to the DMH-vehicle group.However,the AI in the combination treatments,5-FU + CUR(49.05 ± 6.75 vs 41.78 ± 6.92,P = 0.192;49.05 ± 6.75 vs 38.86 ± 4.73,P = 0.771) and 5-FU + HHC(53.69 ± 8.59 vs 41.06 ± 4.81,P = 0.379;53.69 ± 8.59 vs 38.86 ± 4.73,P = 0.245) did not reach significant levels as compared with each treatment alone and 5-FU monotherapy,respectively.CONCLUSION:The combined effects of HHC with 5-FU exhibit a synergistic inhibition by decreasing ACF formation mediated by down-regulation of COX-2 expression.

急性混合细胞白血病40例的临床诊治分析

目的探讨急性混合细胞白血病患者临床诊断及治疗方法,为日后的临床诊治提供参考与指导。方法选择我院2013年1月至2015年9月收治的急性混合细胞白血病患者40例为研究对象,应用随机数字表法分为观察组与对照组,每组20例。两组患者均采用骨髓形态学及细胞化学染色进行诊断。观察组患者给予诱导缓解联合辅助治疗,对照组患者给予巩固治疗,对比两组患者的临床疗效。结果经过临床诊断,两组患者均确诊,无误诊、漏诊。经过临床治疗,观察组患者治疗总有效率为95.0%,高于对照组的70.0%,两组比较,差异有统计学意义(P<0.05)。结论采用骨髓形态学及细胞化学染色诊断急性混合细胞白血病,结果准确;选择诱导缓解+辅助治疗该病临床效果较好,可帮助患者延长生命,降低疾病带来的痛苦,值得临床推广应用。