吉西他滨联合卡培他滨治疗转移性三阴乳腺癌32例临床观察

目的探讨吉西他滨联合卡培他滨治疗转移性三阴乳腺癌的效果。方法对32例转移性三阴乳腺癌予吉西他滨联合卡培他滨方案化疗:吉西他滨1 g/m2静脉滴注,d 1、8;卡培他滨1250 mg/m2口服、2/d,d 1～14,3周为1个周期。2个周期后初步评价疗效,如肿瘤进展更换方案,有效者继续应用至少2个周期,共用4个周期后评价疗效及毒性反应。结果本组完全缓解(CR)1例,部分缓解(PR)13例,稳定(SD)12例,进展(PD)6例,总有效(CR+PR)率43.8%,临床获益(CBR)率为62.5%(20/32),主要毒性反应为骨髓抑制及手足综合征。结论吉西他滨联合卡培他滨治疗转移性三阴乳腺癌近期效果满意,毒性反应低,可作为二线化疗方案。     

卡培他滨联合多西他赛治疗晚期乳腺癌的临床观察

目的观察卡培他滨联合多西他赛治疗晚期乳腺癌的有效性和安全性。方法晚期乳腺癌49例,应用卡培他滨1250 mg/m2,2次/d间歇治疗(2周治疗后停止治疗1周)至少6周,每3周疗程的第1天使用多西他赛75 mg/m2静脉注射。2周期后评价近期疗效和毒副反应。结果 49例晚期乳腺癌总有效率为38.7%,其中CR2例,PR17例。结论卡培他滨联合多西他赛治疗晚期乳腺癌有较好的确切疗效,并且毒性反应小。     

多西紫杉醇联合卡培他滨新辅助化疗13例局部晚期乳腺癌的观察

目的探讨多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌的疗效及安全性。方法 13例局部晚期乳腺癌初治患者,卡培他滨药2500 mg/(m2?d),分早晚2次,餐后30 min口服。连续服用2周,休息1周为1个周期。多西紫杉醇75 mg/m2,静脉输注1 h滴完。21 d为1个周期,2周期后评价疗效。结果 13例局部晚期乳腺癌中治疗后完全缓解4例,部分缓解6例,稳定2例,进展1例,有效率76.92%(10/13),主要不良反应为白细胞减少,发生率为82.33%,其中Ⅲ度占29.61%,没有发现有Ⅳ度。结论多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌疗效确切,不良反应可耐受。     

吉西他滨联合卡培他滨治疗复发转移性乳腺癌的临床观察

目的观察吉西他滨联合卡培他滨治疗复发转移性乳腺癌的临床疗效及不良反应。方法 32例蒽环类及紫杉类药物治疗失败的复发转移性乳腺癌患者接受吉西他滨联合卡培他滨治疗：吉西他滨1 000 mg·m-2,静脉滴注第1,8天;卡培他滨1 250 mg·m-2,口服,2次/日,第1~14天,每21 d为1周期,每2个周期评价疗效,最终观察目的为PFS及药物毒副反应。结果 32例患者中完全缓解（CR）3例,部分缓解（PR）11例,ORR为43.75%;中位PFS达7.5个月。主要不良反应为血液系统毒性：Ⅲ~IV度粒细胞减少发生率为42.5%;手足综合征发生率38.2%,胃肠道反应28.3%,无化疗相关死亡病例。结论吉西他滨联合卡培他滨治疗复发转移性乳腺癌近期疗效肯定,耐受良好,远期疗效有待进一步观察。     

多西他赛联合卡培他滨治疗复发转移性乳腺癌的临床疗效观察

目的观察多西他赛联合卡培他滨治复发转移性乳腺癌的近期临床疗效及其不良反应。方法 32例复发转移性乳腺癌患者应用多西他赛75mg/m2静滴,第1d;卡培他滨1200mg/m2口服,2次/d,第1~14d。21d为1个周期,至少2周期后评价近期临床疗效和不良反应。结果所有患者中CR2例(6.3%),PR15例(46.9%),SD10例(31.3%),PD5例(15.6%);RR为53.1%,CBR为84.4%。不良反应主要为恶心与呕吐、粒细胞减少、手足综合征,多为Ⅰ~Ⅱ度。结论卡培他滨联合多西他赛治疗复发转移性乳腺癌临床疗效确切,不良反应可以耐受,可以作为晚期乳腺癌有效的治疗方案。     

长春瑞滨联合卡培他滨治疗转移性乳腺癌的临床研究

目的观察长春瑞滨联合卡培他滨对紫杉类和/或蒽环类药物治疗后失败的转移性乳腺癌的疗效、安全性。方法39例晚期乳腺癌患者均给予长春瑞滨25mg·m^-2,第一,八天;希罗达口服,950mg·m^-2,1日2次,餐后服用,连续服用14d。21d为1周期,至少完成2周期化疗。每周期评价毒性反应,2周期化疗后评价疗效。结果39例患者有效率达46.2%。无CR病人,PR18例（46.2%）,SD13例（33.3%）,PD8例（20.5%）。中位肿瘤进展时间（TTP）为6.4个月（1～18个月）。最常见的不良反应为手足综合征、骨髓抑制、神经毒性、胃肠道反应等,多为轻度到中度。结论长春瑞滨联合卡培他滨对紫杉类和/或蒽环类药物治疗后失败的转移性乳腺癌有较好的疗效,毒性可以耐受。     

吉西他滨联合卡培他滨治疗老年乳腺癌疗效观察

目的评价吉西他滨联合卡培他滨治疗老年进展期乳腺癌的疗效和毒副反应。方法对32例内分泌治疗无效的晚期乳腺癌患者采用吉西他滨及卡培他滨联合化疗（吉西他滨1000mg/m2,静脉滴注d1、8;卡培他滨800mg/m2,口服,2次/d,d1-14;3周为1周期,至少化疗2个周期后评价疗效和毒副反应。结果完全缓解（CR）2例,部分缓解（PR）18例,总有效率（RR）为62.5%,稳定（SD）7例,中位疾病进展时间（TTP）为7个月,1年生存率61%,主要毒副反应为骨髓抑制和手足综合征,部分患者出现药物性肝损害,均可耐受。结论对老年性乳腺癌,吉西他滨联合卡培他滨治疗是比较好的化疗方案,毒副反应可耐受。     

多西紫杉醇联合卡培他滨治疗原发性晚期乳腺癌疗效观察

目的探讨紫杉醇联合卡培他滨治疗原发性晚期乳腺癌的疗效和毒副作用。方法原发性晚期乳腺癌20例,化疗方案紫杉醇70～80mg/（m^2.d）静脉滴注,第1、8天;卡培他滨1800mg/（m^2.d）分两次口服,第1～14天,每3周为1个周期,连用2个周期,治疗结束2周后评价疗效。结果 20例患者均可评价疗效,RR55%,其中CR3例,PR10例;主要毒副作用为骨髓抑制和胃肠道反应,均可耐受。结论紫杉醇联合卡培他滨治疗原发性晚期乳腺癌疗效肯定、毒副作用可耐受。     

卡培他滨在晚期乳腺癌维持治疗中的临床观察

目的探讨卡培他滨在晚期乳腺癌维持治疗中的疗效及安全性。方法 56例晚期乳腺癌患者,均为经一线含卡培他滨联合化疗4~6周期达缓解或稳定者,依据治疗方法不同分为治疗组与对照组,卡培他滨维持治疗组(35例)患者给予卡培他滨口服1000 mg/m2日2次,d1~14,21 d为1个周期,对照组(21例)患者予以定期随访观察。比较两组患者无进展生存率(PFS)、总生存率(OS)与安全性。结果卡培他滨维持治疗组PFS为8.6个月,高于对照组的6.2个月,差异有统计学意义(P<0.05)。治疗组OS为23.2个月,高于对照组的15.7个月,差异有统计学意义(P<0.05)。卡培他滨治疗组总有效率RR为17.1%(6/35),疾病控制率DCR为68.6%(24/35)。主要不良反应为手足综合征、骨髓抑制及胃肠道反应,均可控制。结论卡培他滨作为晚期乳腺癌一线联合化疗后的维持治疗用药,可延长患者生存期,不良反应可耐受,依从性好。     

卡培他滨联合顺铂治疗晚期乳腺癌的临床观察

目的探讨卡培他滨联合顺铂治疗晚期乳腺癌的临床治疗效果。方法选取2008年6月至2011年4月在我院接受治疗的晚期乳腺癌病例90例,给予口服卡培他滨进行治疗,每天给予2500mg/m2,早晚各一次,服用14d后休息7d为1个治疗周期;同时每个周期第1-3天静脉滴注顺铂60mg/m2,所有的患者均治疗2个周期以上,观察患者的临床治疗效果和药物的毒副反应。结果 CR 6例,PR 32例,NC23例,PD29例,有效率为42.22%。患者出现毒性反应多为轻中度,经对症治疗后均很快好转。主要的毒性反应包括手足综合征、白细胞、血小板以及血色素减少、肝肾功能损害、腹泻以及恶心呕吐等,过敏反应病2例。结论卡培他滨联合顺铂治疗晚期乳腺癌疗效较好,使用方便,安全性高且毒性反应较轻,是治疗晚期乳腺癌比较理想的治疗方案。     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.