XELOX方案与FOLFOX方案治疗101例晚期大肠癌的临床观察

目的:比较奥沙利铂联合卡培他滨(XELOX方案)与奥沙利铂联合氟尿嘧啶+亚叶酸钙(FOLFOX方案)治疗晚期大肠癌近期疗效和不良反应。方法:101例晚期大肠癌患者随机分成XELOX组54例和FOLFOX组47例进行化疗。XELOX方案:奥沙利铂130 mg.m-2,静脉滴注,d1;卡培他滨2 500 mg.m-2.d-1,分早晚2次口服,d1～14。FOLFOX:奥沙利铂130 mg.m-2,静脉滴注,d1;氟尿嘧啶400 mg.m-2,静脉注射,d1;氟尿嘧啶2.4～3 g.m-2,静脉持续输注46 h,d1,2;亚叶酸钙200 mg.m-2,静脉滴注,d1。每3周重复。结果:XELOX方案总有效率(CR+PR)为46.30%,中位疾病进展时间7.8个月,中位生存期13.5个月。FOLFOX方案总有效率(CR+PR)为42.6%,中位疾病进展时间6.5个月,中位生存期11.8个月。2组疗效比较,差异无统计学意义(P>0.05)。结论:2种方案治疗晚期大肠癌有效率近似,不良反应均可耐受,但XELOX方案的耐受性、患者依从性更好。     

XELOX方案与FOLFOX4方案治疗晚期结直肠癌75例

目的：比较奥沙利铂联合卡培他滨(XELOX)方案与奥沙利铂联合5-氟尿嘧啶/亚叶酸钙（5-FU/LV）(FOLFOX4)方案治疗晚期结直肠癌的近期疗效和毒副反应。方法：75例转移或复发晚期结直肠癌患者随机分为两组：奥沙利铂联合卡培他滨组(XELOX组,A组)37例,奥沙利铂联合5-FU/LV组(FOLFOX4组,B组)38例。A组给予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000mg[DK]?m-2,po,bid,d1~14;奥沙利铂130mg[DK]?m-2,静脉点滴,d1;1周期21d。B组给予5-FU,LV联合奥沙利铂方案化疗,奥沙利铂85mg[DK]?m-2,静脉点滴,d1;LV 200mg[DK]?m-2,静滴2h后予5-FU 400mg[DK]?m-2,推注,后续600mg[DK]?m-2持续静滴22h,d1,2;每2周重复1次,4周为1周期。两组患者均治疗2周期以上。按WHO标准评价客观疗效和毒副反应。结果：两组共75例患者均可评价疗效。A组：完全缓解（CR）3例,部分缓解（PR）15例,有效率(CR+PR)为48.6%;疾病进展时间(TTP)为6.12个月,生存时间(MST) 为13.7个月。B组：CR 3例,PR 16例,有效率为50.0%,TTP为5.91个月,MST为13.9个月。所有毒副反应都能耐受,A组消化道反应、血液学毒性、口腔炎、脱发的发生率显著低于B组(P<0.05);两组周围神经毒性和血小板减少发生率相近;A组的手足综合征发生率明显高于B组(P<0.05),但程度较轻,主要为Ⅰ~Ⅱ度。结论：XELOX方案与FOLFOX4方案的治疗晚期结直肠癌疗效相近,但XELOX方案具有用药更为方便,安全性更好等优点,值得临床一线使用。     

XELOX方案辅助化疗治疗老年结直肠癌的疗效评估

目的:观察希罗达联合奥沙利铂(XELOX)治疗老年性晚期结直肠癌的疗效及安全性。方法:将我院2005年4月～2009年10月间收治的164例老年晚期转移性结直肠癌患者随机分为两组,治疗组为XELOX组82例,予卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m2,口服,2次/d,第1～14 d;奥沙利铂130 mg/m2,静脉点滴,第1 d;21 d1周期。对照组为FOLFOX4组82例,予5-氟尿嘧啶,亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m2,静脉点滴,第1 d;亚叶酸钙200 mg/m2,静滴2 h后予5-氟尿嘧啶400 mg/m2,推注,后续600 mg/m2,持续静滴22 h,第1、2 d;每2 w重复,4 w为1周期。两组均治2周期以上。按WHO标准评价客观疗效和不良反应。结果:164例患者均完成化疗疗程。XELOX组总有效率49.2%,临床控制率为81.7%,其中完全缓解8例(9.8%),部分缓解32例(39.4%),病情稳定27例(32.9%),病情进展15例(18.3%)。中位进展时间为8.2个月。FOLFOX4组总有效率43.9%,临床控制率为78.0%,其中完全缓解7例(8.5%),部分缓解29例(35.4%),病情稳定28例(34.1%),病情进展18例(22.0%)。中位进展时间为7.9个月。两组近期有效率无明显统计学差异。不良反应比较,手足综合症以XELOX组显著(P<0.05),恶心呕吐发生率以FOLFOX4组高(P<0.05),XELOX方案中的中性粒细胞减少和神经毒性发生率分别为8.5%和2.4%,显著低于FOLFOX4方案的47.6%和46.3%(P<0.01)。结论:XELOX方案与FOLFOX4方案的疗效近似,但XELOX方案用药更为方便,安全性更好。值得推广应用。     

奥沙利铂和伊立替康治疗晚期大肠癌的近期临床疗效对比观察

目的对比分析研究FOLFOX4和FOLFIRI方案治疗初治晚期大肠癌的近期临床疗效及不良反应。方法收集晚期大肠癌患者53例,随机分为FOLFOX4组26例和FOLFIRI组27例,分别采用奥沙利铂+亚叶酸钙+5-氟脲嘧啶方案和伊立替康+亚叶酸钙+5-氟脲嘧啶方案进行化疗,以2周为1周期,4~6周期后评定和对比两组临床疗效及不良反应。结果 FOLFOX4组和FOLFIRI组治疗后近期疗效总有效率分别为为46.15%和40.74%,无统计学意义;FOLFOX4组末梢神经毒性发生率显著高于FOLFIRI组(P<0.05),腹泻发生率FOLFOX4组显著低于FOLFIRI组(P<0.05)。结论应用FOLFOX4和FOLFIRI方案治疗初治晚期大肠癌的近期临床疗效相当,毒副作用较少,均可作为晚期结直肠癌化疗方案的首选。     

晚期结直肠癌的维持治疗

结直肠癌在恶性肿瘤中发病率居第3位,且近年来呈逐步上升趋势,是严重威胁人类健康的主要恶性肿瘤。晚期结直肠癌的一线化疗目前以FOLFOX、XELOX和FOLFIRI等方案为标准方案,但对于化疗获益后患者的后续治疗,是"生命不息、化疗不止",还是病情稳定就停止化疗,一直以来都存在争议。     

亚叶酸钙加氟尿嘧啶联合奥沙利铂治疗晚期胃癌26例

目的 :探讨亚叶酸钙加氟尿嘧啶 (5 Fu)持续 72h滴注联合奥沙利铂治疗晚期 /转移性胃癌的临床疗效和毒副作用。方法 :共入选 2 6例。治疗方案为 :在每周期的d1,静脉滴注奥沙利铂 130mg·m-2 ;d1～d3静脉滴注亚叶酸钙 2 0 0mg·m-2 ·d-1;在d1静脉滴注亚叶酸钙结束后 ,静脉注射 5 Fu 0 .75 g ,然后静脉滴注 5 Fu 3.0g·m-2 ,持续 72h(d1～d3)。 4周为 1个周期 ,每例患者至少应用 2个周期。结果 :2 6例晚期胃癌患者获CR 2例 ,PR9例 ,有效率 4 2 .3%。毒副作用主要为骨髓抑制、口腔黏膜炎、腹泻 ,无严重神经损害。结论 :此方法治疗晚期 /转移性胃癌疗效好 ,安全性高。     

伊立替康联合5-氟尿嘧啶/亚叶酸钙双周方案治疗晚期结直肠癌的临床观察

目的:观察伊立替康(CPT-11)联合5-氟尿嘧啶(5-Fu)/亚叶酸钙(LV)方案治疗晚期结直肠癌的疗效及毒副反应。方法:全组31例,可评价疗效者30例,全部采用双周方案:CPT-11180mg·m-2静脉滴注,第1天;LV200mg·m-2静脉滴注,第1、2天;5-Fu400mg·m-2静脉推注,随后5-Fu600mg·m-2静脉滴注22h,第1、2天。14d为1个周期,3个周期(6周)评价疗效。结果:完全缓解1例,部分缓解11例,缓解率达40%;疾病稳定14例,疾病进展4例。中位疾病进展时间为6.5个月,中位生存期为13.9个月。主要毒副反应为迟发性腹泻(Ⅲ/Ⅳ度发生率为30%)及中性粒细胞减少(Ⅲ/Ⅳ度发生率为26.6%)。结论:CPT-11联合5-Fu/LV方案治疗晚期结直肠癌有效率高,毒副反应可以耐受,可作为晚期结直肠癌的一线或二线化疗方案。     

奥沙利铂的两组化疗方案治疗远处转移性结直肠癌的成本-效果分析

目的 评价FOLFOX与XELOX方案治疗远处转移性结直肠癌的经济学效果.方法 105例患者入组,其中FOLFOX方案组69例,接受每3周1个疗程的奥沙利铂+亚叶酸钙+5-氟尿嘧啶持续静脉注射的FOLFOX治疗方案;XELOX组36例,接受每3周1个疗程的奥沙利铂+卡培他滨治疗方案.评价2组的疗效及不良反应,并进行成本-效果分析.结果 FOLFOX和XELOX组总有效率分别为58.0%和41.7%,总成本分别为15914.25和22239.26元;成本一效果比分别为274.39和533.31,因FOLFOX治疗方案成本低而效果高于XELOX方案,故无需进行增量成本分析.FOLFOX组胃肠道不良反应发生率明显高于XELOX组(78.3%vs.33.3%),差异有显著性(P＜0.05).结论 FOLFOX方案治疗转移性结直肠癌的成本-效果优于XELOX方案.但其胃肠道不良反应发生率较高,同时持续注射给药给患者带来较多不便.     

贝伐珠单抗联合FOLFOX4化疗方案治疗晚期转移性结直肠癌的临床研究

目的 探讨贝伐珠单抗(Avastin)联合奥沙利铂(L-OHP)+5-氟尿嘧啶(5-FU)+亚叶酸钙(LV)(FOLFOX4)治疗晚期转移性结直肠癌(MCC)的临床疗效与安全性。方法 入选2011年4月至2013年12月武警浙江总队嘉兴医院收治的MCC患者84例,其中用贝伐珠单抗联合FOLFOX4方案治疗者39例,单纯用FOLFOX4方案化疗者45例。FOLFOX4化疗方案:第1天,奥沙利铂85mg·m-2静脉滴注2 h;第1,2天,亚叶酸钙200 mg·m-2静脉滴注,2 h;5-氟尿嘧啶400 mg·m-2静脉推注,第1,2天;5-氟尿嘧啶600 mg·m-2静脉滴注,第1,2天;贝伐珠单抗方案:贝伐珠单抗10 mg·kg-1+0.9%氯化钠注射液100 m L静脉滴注1 h(第1次应用时为90 min),每2周1次。2组患者均接受2个周期化疗后,比较近期临床疗效及其化疗相关不良反应发生率。结果 贝伐珠单抗+FOLFOX4组客观有效率和疾病控制率均显著高于FOLFOX4组,且差异有统计学意义(P<0.05);2组患者Ⅲ~Ⅳ级恶心呕吐、粒细胞下降及血小板下降等药品不良反应发生率比较,差异无统计学意义(P>0.05)。结论 FOLFOX4联合贝伐珠单抗可显著提高晚期转移性结直肠癌的近期临床疗效,且不增加化疗相关不良反应。     

伊立替康联合氟尿嘧啶、亚叶酸钙二线治疗晚期结直肠癌的临床观察

目的:观察FOLFIRI方案二线治疗晚期结直肠癌的疗效及安全性。方法:28例FOLFOX4化疗失败的患者,改用FOLFIRI方案挽救化疗。结果:完全缓解为0例,部分缓解6例,稳定16例,进展6例,有效率21.4%。不良反应主要为恶心、呕吐、白细胞减少和延迟性腹泻。结论:FOLFIRI方案二线治疗晚期结直肠癌,疗效肯定,不良反应可控制。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.