顺铂加吉西他滨与顺铂加长春瑞滨一线治疗晚期非小细胞肺癌的对照研究

目的:探讨顺铂(DDP)加吉西他滨(GEM)与顺铂加长春瑞滨(NVB)治疗晚期非小细胞肺癌(NSCLC)的疗效、不良反应。方法:66例NSCLC患者分别接受GEM/DDP方案与NVB/DDP方案化疗GEM/DDP(GP)化疗方案:GEM1000mg.m-2d1、8DDP75mg.m-2,总剂量分为3d使用,dl~3NVB/DDP(NP)化疗方案:NVB25mg.m-2d1、8;DDP80mg.m-2,总剂量分为3d使用,d1~3。21d为一周期,所有病例均接受2个周期以上的治疗。观察两组的近期有效率、中位生存时间(MST)、1年生存率、不良反应。结果:GP和NP方案的有效率分别为41.6%和36.7%,中位生存期分别为10.3个月和9.6个月,1年生存率分别为44.4%和40.0%(P=0.33)。GP组的III~IV级血小板减少47.2%,显著高于NP组6.6%(P<0.01),而NP组的中性粒细胞减少高于GP组,分别为60%和33.3%(P<0.05)。结论:GP和NP方案治疗晚期NSCLC疗效相当,但毒性反应略有差别。     

康莱特注射液联合NP方案治疗晚期非小细胞肺癌临床疗效观察

目的 观察康莱特注射液(KLT)联合化疗对晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的治疗效果.方法 试验组:采用异长春花碱(NVB) 顺铂(DDP)方案化疗2个周期,同时加用康莱特注射液200 ml/d静脉滴注,21 d为1个疗程,共2个疗程.对照组单用NVB DDP.结果 两组有效率分别为59.0%(23/39)和36.6%(15/41)P＜0.05,差异显著;试验组骨髓抑制发生率为23.1%(9/39),而对照为43.9%(18/41),P＜0.05,差异显著;试验组消化道不良反应发生率为12.8%(5/39),对照组为24.4%(10/41),P＜0.05,差异显著;试验组治疗前后KPS评分及体质量评分明显高于对照组,P＜0.01,差异非常显著.结论 康莱特联合NP方案化疗可提高化疗的疗效,减轻化疗的不良反应,使患者的生存质量得到改善.     

重组人血管内皮抑素联合多西紫杉醇方案治疗非小细胞肺癌的临床疗效

目的 评价重组人血管内皮抑素(YH-16)联合周剂量多西紫杉醇治疗晚期非小细胞肺癌(NSCLC)的近期临床疗效及安全性.方法 46例晚期复发的NSCLC患者分为治疗组(21例,YH-16+周剂量多西紫杉醇)和对照组(25例,单用多西紫杉醇周剂量方案).治疗2～4个周期,按照RECIST标准和NCI-CTC3.0标准分别评价其疗效及毒副反应.结果 治疗组和对照组有效率分别为19.0％和8.3％(P＞0.05),疾病控制率为61.9％和54.2％(P＞0.05).治疗组中位无进展生存期(PFS)明显长于对照组(5.4个月vs.4.5个月)(P＜0.01).两组近期常见的毒副反应相仿(P＞0.05).结论 YH-16联合多西紫杉醇治疗晚期NSCLC能提高患者的无进展生存期,且毒副反应无明显增加.     

参芪扶正注射液联合NP方案治疗晚期非小细胞肺癌的疗效观察

目的观察参芪扶正注射液联合NP方案在晚期非小细胞肺癌(NSCLC)中的疗效。方法所有病例均经病理和(或)细胞学确诊为晚期NSCLC。其中:治疗组42例行长春瑞滨(NVB)加顺铂(DDP)方案化疗,同时加用参芪扶正注射液;对照组26例单用NP化疗。参芪扶正注射液250ml, d1-10;NVB25mg/m2,d1,d8;DDP:30mg/m2d2-4,均静脉滴注。结果治疗组和对照组的总RR分别为28．6％和19．2％(P=0．003),总临床受益率(CBR)分别为71．4％和61．5％(P=0．0032),中位进展时间分别为6．2个月和4．9个月(P=0．06),治疗组与对照组化疗后的生活质量(QOL)评分比较有明显提高(P=0．008),毒副反应亦较轻(P=0．006)。结论参芪扶正注射液能明显改善晚期NSCLC的RR、CBR、QOL,并且能增效减毒,具有良好的应用价值。     

治疗晚期非小细胞肺癌NP化疗方案观察

目的：观察NP(NVB、DDP)方案治疗晚期NSCLC临床疗效及不良反应。方法：NVB(去甲长春花碱)25mg／m^2 iv 10min，d1、8；DDP(顺铂)800mg／m^2 d1静点，治疗晚期NSCLC38例。结果：CR3例．PR17例．总有效率为52．6％。主要不良反应为白细胞减少．发生率为92．8％，其中Ⅲ～Ⅳ度骨髓抑制占64．2％。结论：NP方案治疗晚期NSCLC疗效明确，血骨髓抑制明显。     

顺铂不同剂量联合长春瑞滨治疗非小细胞肺癌的临床研究

目的:对比研究顺铂(DDP)不同剂量联合长春瑞滨(NVB)在非小细胞肺癌(NSCLC)患者化疗中的疗效和不良反应。方法:123例Ⅲ～Ⅳ期NSCLC患者,采用不同剂量DDP联合长春瑞滨进行分组对照研究,分为低剂量DDP组(n=67)与高剂量DDP组(n=56)。低剂量DDP组给予NVB25mg.m-2,静脉滴注,第1、8天;DDP20mg.m-2,静脉滴注,第1～5天。高剂量DDP组给予NVB25mg.m-2,静脉滴注,第1、8天;DDP60mg.m-2,静脉滴注,第1～2天。21d为一周期。化疗2周期后评定疗效。结果:高剂量DDP组与低剂量DDP组的有效率分别为41.1%、28.4%(P>0.05);高剂量DDP组白细胞减少总发生率为87.5%,明显高于低剂量DDP组的71.6%(P<0.05);2组Ⅲ～Ⅳ度白细胞减少发生率无显著性差异(P>0.05)。结论:DDP高剂量组与低剂量组的临床疗效相当。高剂量顺铂组毒性反应的发生率显著高于低剂量组,但严重毒性反应的发生率相近。     

参芪扶正注射液联合NP方案治疗晚期非小细胞肺癌临床疗效观察

目的观察参芪扶正注射液联合NP方案化疗对晚期非小细胞肺癌（non-small cell lungcancer,NSCLC）的治疗效果。方法试验组：采用异长春花碱（NVB）＋顺铂（DDP）方案化疗2个周期,同时加用参芪扶正注射液250 ml/d静脉滴注,21 d为1个疗程,共2个疗程。对照组单用NVB＋DDP。结果两组有效率分别为44.7%（14/38）和34.1%（14/41）,P〉0.05,差异无显著性;治疗组骨髓抑制发生率为36.8%（14/38）,而对照组为75.6%（31/41）,P〈0.05,差异有显著性;治疗组消化道不良反应发生率为34.2%（13/38）,对照组为87.8%（36/41）,P〈0.05,差异有显著性;治疗组治疗前后KPS评分及体质量评分明显高于对照组,P〈0.01,差异有显著性。结论参芪扶正注射液联合NP方案化疗可提高化疗的疗效,减轻化疗的不良反应,使患者的生存质量得到改善。     

化疗配合中药治疗老年人晚期非小细胞肺癌

目的 观察比较长春瑞宾(NVB)联合顺铂(DDP)组成的NP方案与NP方案配合中药治疗老年晚期非小细胞肺癌(NSCLC)的疗效和安全性.方法 48例老年晚期NSCLC患者随机分为NP组和NP 中药组进行化疗.结果 NP 中药组有效率58.3%,NP组有效率33.3%,两组有显著性差异(P＜0.05).两组生存时间比较,NP 中药组生存率明显高于NP组(P＜0.05).两组剂量限制毒性均为骨髓抑制,白细胞下降占100%,其中白细胞Ⅲ～Ⅳ度下降,NP 中药组为45.8%,NP组为58.3%.消化道反应可以耐受.结论 NP方案配合中药治疗老年晚期NSCLC的疗效高于NP方案.     

艾迪联合吉西他滨与顺铂化疗方案治疗晚期非小细胞肺癌的回顾性研究

目的：评价艾迪联合吉西他滨与顺铂化疗方案（ GP）治疗晚期非小细胞肺癌（ NSCLC）的临床疗效和安全性。方法收治晚期NSCLC患者69例,单用GP化疗为对照组（36例）：吉西他滨1000 mg· m-2,iv,d 1,8;顺铂30 mg· m-2,iv, d 2～4;GP联合艾迪化疗方案作为试验组（33例）,在GP方案基础上,加艾迪50 mL,iv,qd,10 d,均化疗4个周期,评价2组患者化疗临床疗效及不良反应。结果试验组客观有效率（30.3％）明显高于对照组（12.1％）（P＜0.05）;试验组胃肠道反应及血液学毒性等化疗相关不良反应明显低于对照组（ P＜0.05）。结论艾迪联合GP化疗方案治疗晚期NSCLC可以显著提高临床疗效,降低不良反应。     

非小细胞肺癌四种化疗方案的成本效果分析及流行病学临床评价

目的 研究非小细胞肺癌(non-small cell lung cancer,NSCLC)的四种不同化疗方案的药物经济学效果和流行病学临床评价.方法 采用回溯法筛选了129例非小细胞肺癌病例,分成4组,分别为Ⅰ组NP方案(长春瑞滨NVB 顺铂DDP);Ⅱ组GP(吉西他滨GEM 顺铂DDP);Ⅲ组NPA方案(长春瑞滨NVB 顺铂DDP 艾迪AIDI);Ⅳ组NPK(长春瑞滨NVB 顺铂DDP 薏苡仁提取物(康莱特KLT)).运用药物流行病学的疗效比较和药物经济学的成本-效果分析方法进行研究.结果 4组疗效分别为31.43%,36.36%,41.94%,53.33%.不良反应Ⅳ和Ⅲ组低于Ⅰ和Ⅱ组.生活质量Ⅳ＞Ⅲ＞Ⅱ＞Ⅰ组.成本效果比分别为550.22、556.48、641.43、511.58元.结论 NP方案总成本最低但疗效也最低,NPK方案疗效最好,并且每提得一个疗效百分点其花费最小,最具经济学意义.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.