GP方案动静脉联合化疗治疗晚期胰腺癌的临床研究

目的观察吉西他滨+顺铂区域动脉灌注化疗结合静脉化疗治疗晚期胰腺癌的疗效。方法 43例晚期胰腺癌采用区域动脉灌注吉西他滨1 000 mg.m-2加顺铂30 mg.m-2,结合顺铂30 mg.m-2静脉滴注2～3 d,吉西他滨1 000 mg.m-2静脉滴注8 d,每3周为一周期。结果 43例患者,有效率(CR+PR)为30.2%,临床受益率(CBR)为76.7%,中位生存期为14.6月,中位疾病进展时间(TTP)为6.7月。结论 GP方案动静脉联合化疗治疗晚期胰腺癌疗效较高而且毒副反应可以接受。     

盖诺加顺铂联合化疗治疗晚期非小细胞肺癌疗效观察

目的：观察国产长春瑞滨（盖诺）加顺铂联合化疗治疗晚期非小细胞肺癌的近期疗效。方法：对50例晚期非小细胞肺癌（NSCLC）采用盖诺加顺铂方案化疗，21天为1周期，治疗2周期以上评定疗效。结果：50例中PR22例，占44．00％；NC21例，占42．00％；PD6例，占12．00％，有效率（CR＋PR）为44．00％，中位生存期8个月。Ⅲ度白细胞下降30％（15/50），Ⅳ度10％（5／50）。结论：盖诺加顺铂是治疗晚期非小细胞癌一个很有价值的方案，不良反应小，患者可以耐受，值得推广。     

诺维本和顺铂治疗晚期非小细胞肺癌近期疗效

目的观察诺维本和顺铂联合化疗治疗晚期非小细胞肺癌的近期临床疗效.方法 56例晚期非小细胞肺癌应用诺维本25mg/m2,静注第1,8天,顺铂30mg/m2,静注第1～3天,联合化疗.结果初治34例中CR+PR18例,有效率52.9%,复活22例中CR+PR9例,有效率41%,总有效率为48.2%,主要副反应是骨髓抑制及静脉炎,采用深静脉注药以减轻静脉炎的发生.结论诺维本和顺铂联合化疗治疗晚期非小细胞肺癌疗效较高,副反应基本可以接受.     

长春瑞滨联合顺铂治疗148例晚期非小细胞肺癌疗效观察

目的:观察国产长春瑞滨(NVB)联合顺铂(DDP)治疗晚期非小细胞肺癌(NSCLC)的疗效.方法:盖诺25 mg/m2,d1.8;DDP40 mg/m2,d1,2,21～28天为1周期,至少治疗2周期.结果:CR 15例,PR 56例,SD 46例,PD 31例,有效率为44%.不良反应主要为骨髓抑制和消化道反应.结论:NVB加DDP联合化疗治疗晚期NSCLC疗效较高,不良反应可耐受,可作为晚期NSCLC一线治疗方案.     

盖诺联合顺铂治疗初治非小细胞肺癌的疗效观察

目的评价盖诺（长春瑞滨,NVB）联合顺铂（顺氯氨铂,DDP）治疗初治非小细胞肺癌（NSCLC）近期疗效和毒副作用。方法对北京市平谷区医院近4年来84例初治晚期（Ⅲb-Ⅳ）非小细胞肺癌采用盖诺联合顺铂化疗（NP方案）,盖诺25mg/m2·d,d1.8;顺铂25mg/m2·d,d3～5,每3周重复一次,完成3周期或以上评价疗效。结果总有效率34.5%,主要毒副作用是骨髓抑制和消化道反应。结论盖诺联合顺铂治疗晚期非小细胞肺癌疗效确切,毒副反应可耐受,骨髓抑制为其剂量限制性毒性。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌疗效观察

目的 观察吉西他滨与顺铂联合化疗治疗晚期非小细胞肺癌的疗效和不良反应.方法 吉西他滨1000 mg/m2第1、8天静脉滴注并联合顺铂治疗晚期非小细胞肺癌50例,3周为1个治疗周期,2个周期后评价疗效和毒副作用.结果 50例均化疗2个周期以上,其中完全缓解(CR)1例,部分缓解(PR)20例,稳定(SD)19例,进展(PD)10例,缓解率(CR+ PR)42％.结论 吉西他滨联合顺铂治疗晚期非小细胞肺癌具有较好的疗效,且不良反应轻,患者可耐受.     

吉西他滨联合长春瑞宾双周非含铂方案治疗晚期非小细胞肺癌初步报告

目的观察吉西他滨(择菲)联合长春瑞宾(盖诺)双周非含铂方案治疗晚期非小细胞肺癌的疗效与安全性。方法对于晚期非小细胞肺癌患者,第1天静脉注射吉西他滨1000mg/m2,第1天静脉注射盖诺25mg/m2,每2周重复,至少用4周期以上,如果SD、CR或PR,则继续用药,可用至8周期。化疗结束后2周评价疗效。结果共入组晚期小细胞肺癌30例,均可评价疗效,有效率(CR+PR)36.7%(11/30例),中位生存时间10.7月,一年生存率33.3%。主要毒性为Ⅲ￣Ⅳ°白细胞下降23.3%,Ⅲ￣Ⅳ°血小板下降13.3%,Ⅲ￣Ⅳ°恶心呕吐6.7%。结论吉西他滨(择菲)联合长春瑞宾(盖诺)双周非含铂方案治疗晚期小细胞肺癌的疗效与文献报道含铂方案的疗效大致相同,毒性反应较轻,是治疗晚期小细胞肺癌的有效方案。     

国产吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床观察

目的 观察国产吉西他滨(GEM)联合顺铂(DDP)治疗晚期非小细胞肺癌的近期疗效、毒副反应、中位生存期及耐受性.方法 国产吉西他滨1 000 mg·m-2,静脉滴注30 min,第1、8 天;顺铂60～70 mg·m-2,静脉滴注,分3～ 4 d应用,28 d为一个周期,治疗39 例晚期非小细胞肺癌患者.结果 39 ...     

吉西他滨联合顺铂治疗晚期非小细胞肺癌

目的观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副作用。方法选择晚期非小细胞肺癌患者37例,给予吉西他滨1000－1250mg／m2,静滴,第1天及第8天;顺铂80mg／m2,静滴,第1天或分第1—3天。21d为1周期,至少完成2周期。结果全组完全缓解（CR）0例,部分缓解（PR）16例,稳定（sD）13例,总有效率（CR＋PR）43．2％,肿瘤控制率（CR＋PR＋SD）78．4％。毒副作用主要是骨髓抑制及恶心、呕吐。结论吉西他滨联合顺铂治疗晚期非小细胞肺癌安全有效,毒副作用可以耐受。     

多帕菲联合顺铂化疗在局部晚期非小细胞肺癌中的应用评价

目的探讨多帕菲(docetaxel)联合顺铂(DDP)方案治疗局部晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法选取初治晚期非小细胞肺癌43例,采用多帕菲加顺铂方案联合化疗,多帕菲按总量150 mg·m-2静滴分第1,2天;顺铂按75mg·m-2分3 d静滴,即第3,4,5天,21 d为一周期;按WHO疗效及不良反应评价标准,完成2～3个周期治疗的患者进行临床疗效及不良反应评估.结果可评价患者43例,其中完全缓解(CR)5例占11.6%(5/43),部分缓解(PR)19例占44.2%(19/43),总有效(CR PR)为占55.8%(24/43),中位生存期为9.2个月,1年生存率40%(16/40).全组不良反应主要为血液学毒性,其中白细胞降低发生率为51.16%(22/43),血小板下降发生率为9.3%(4/43),血红蛋白下降发生率为4.7%(2/43),非血液学毒性有胃肠道反应和脱发等.结论多帕菲联合顺铂治疗晚期非小细胞肺癌较好疗效,不良反应可耐受,安全性高,可在临床推广应用.     

alpha-glucosidase (CHO) (Genzyme)

Genzyme General is developing recombinant human alpha-glucosidase, produced in mammalian cell culture, as a potential treatment for Pompe disease. By July 2004, enrollment was completed in two clinical trials and an observational study in adults. Genzyme was planning to file for regulatory approval in Europe during 2004, followed by filings in the US and Japan in mid-2005.     

(S)-oxybutynin (Sepracor)

Sepracor is developing (S)-oxybutynin, a single-isomer version of Alza's Ditropan (racemic oxybutynin), a muscarinic acetylcholine receptor antagonist, as a potential treatment for urinary incontinence.     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic

Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.     

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.     

4（R）—（6—氨基—9H—嘌呤—9—基）—2（R）—（羟甲基）四氢呋喃—3（R）—醇的合成

为寻找抗HIV化合物,我们以D－核糖为原料,经甲基化、硅烷基化、还原裂解反应制得重要中间体1－脱氧核糖（5）,再通过形成环状亚砜化合物,与NaN3发生反应后,经过还原、缩合、环合、氨化、脱保护基反应制得异脱氧腺嘌呤核苷（1）,各步反应收率均超过70％。其抗HIV活性测定尚在进行中。     

1,2-环己二胺柠檬酸铂(Ⅱ)及异柠檬酸铂(Ⅱ)的合成和抗癌活性

报道了1,2-环己二胺异柠檬酸铂(Ⅱ)及1,2-环己二胺柠檬酸铂(Ⅱ)的合成及鉴定方法。抗癌试验表明前者在40及80mg/kg 剂量下对小鼠 L1210、P388及S180均有明显的抑瘤作用,且有部分动物可治愈;后者对 L1210也有明显的抑瘤作用,但较前者为弱。     

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.     

4（R）—（6—氨基—9—嘌呤基）—2（R）—（羟甲基）四氢呋喃—3（R）—醇的合成

为寻找抗免疫缺陷病毒化合物,以D－核糖为原料,经甲基化、硅烷基化、还原裂解反应制得重要中间体1－脱氧核糖（5）,再通过形成环状亚砜化合物,与NaN3发生反应后,经过还原、缩合、环合、氨化、脱保护基反应制得异脱氧腺嘌呤核苷（1）,各步反应收率均超过70％。