化疗药物对细胞因子诱导的杀伤细胞(CIK)的影响

探讨化疗药物及地塞米松对CIK细胞增殖活性及淋巴细胞亚群的影响。分别选取不同浓度顺铂、氟尿嘧啶、紫杉醇和地塞米松与不同诱导天数的CIK细胞共培养,在加入或不加入IL-2的情况下,采用MTT法检测各种药物对CIK细胞增殖活性的影响,流式细胞术检测CIK细胞中各亚群的比例。顺铂、氟尿嘧啶、紫杉醇及地塞米松均在一定程度上抑制CIK细胞的增殖活性,其中顺铂和紫杉醇表现出明显的剂量依赖性(P0.05);IL-2可对CIK细胞产生保护作用,在一定程度上降低化疗药物对CIK细胞的抑制作用(P0.05)。顺铂主要降低CD3+CD56+亚群比例(P0.05),对CD3+CD4+、CD3+CD8+亚群比例无显著影响(P0.05)。     

PNAS：用于增强顺铂化疗功效的纳米粒

近日。佐治亚大学研究人员对传统化疗药物顺铂进行修改,开发出一种前体药物,能显著加强顺铂瞄准并摧毁癌细胞的能力。最新科学家成功制造出顺铂的修改版本,称为铂-M（Platin—M）,铂-M目的是通过攻击癌细胞线粒体来克服这种耐药性。相关研究发表在PNAS杂志上。     

化疗药物对人胃癌SGC-7901细胞系端粒酶活性影响

目的　研究常见化疗药物对人胃癌SGC 790 1细胞系端粒酶活性影响。方法　MTT (噻唑蓝 )法测定化疗药物顺铂、丝裂霉素、阿霉素、 5 氟尿嘧啶、氟铁龙 (脱氧氟尿苷 )对人胃癌SGC 790 1细胞系毒性作用的半数抑制(IC5 0 )浓度 ;用TRAP ELISA法测定 4 0×IC5 0浓度化疗药物作用于SGC 790 1细胞 4h、 2 8h端粒酶活性及IC5 0浓度IC5 0化疗药物作用于SGC 790 1细胞 2 4h、 72h、 12 0h细胞端粒酶活性。结果　高浓度 ,低浓度顺铂、丝裂霉素对SGC 790 1细胞端粒酶活性有完全抑制作用 ;而阿霉素、 5 氟尿嘧啶、氟铁龙对SGC 790 1细胞端粒酶活性有部分抑制作用。结论　阿霉素、 5 氟尿嘧啶、氟铁龙对SGC 790 1细胞端粒酶活性有轻度抑制作用 ;顺铂、丝裂霉素能完全抑制端粒酶活性 ,呈时间浓度效应     

不同化疗方案联合手术治疗非小细胞肺癌的临床疗效及对患者免疫功能的影响分析

目的:探讨分析不同化疗方案联合手术治疗非小细胞肺癌的临床疗效以及对患者免疫功能的影响。方法:经病理学证实的非小细胞肺癌患者94例,随机数字表法将其分为顺铂组与洛铂组,各47例。2组患者均采取手术治疗,并术前行辅助化疗。其中顺铂组采取紫杉醇+顺铂方案,洛铂组接受紫杉醇+洛铂方案。比较治疗前后2组患者临床疗效及KPS评分,并对Ig A、Ig G、Ig M、CD4+及CD8+指标水平进行分析。结果:洛铂组有效率(CR+PR)为87.2%(41/47),与顺铂组[80.8%(38/47)]差异无统计学意义(P0.05)。洛铂组术后KPS评分及CD4+水平高于顺铂组(P0.05),但CD8+水平低于顺铂组(P0.05),差异有统计学意义;2组患者手术前后Ig A、Ig G及Ig M均无统计学意义(P0.05)。洛铂组毒副反应发生率低于顺铂组(P0.05)。结论:含洛铂术前辅助化疗方案有助于改善非小细胞肺癌患者的免疫功能,降低化疗的毒副反应。     

妇科卵巢恶性肿瘤腹腔灌注化疗患者的护理

腹腔灌注化疗已成为治疗妇科肿瘤的有效方法之一。特别是卵巢肿瘤,无论是早期还是晚期,手术治疗后均采用以铂类为基础的腹腔内化疗,增加了肿瘤与药物接触,可减少抗肿瘤药所致的全身不良反应,减轻痛苦,提高恶性肿瘤患者的生存质量和治疗效果。现将我院妇科2009年1月～2010年1月收治的36例卵巢恶性肿瘤患者术后腹腔灌注化疗的护理体会报告如下。     

小剂量顺铂动脉化疗联合放疗对中晚期宫颈癌的临床疗效

目的:探讨小剂量顺铂用于子宫动脉化疗联合放疗治疗中晚期宫颈癌的临床疗效。方法:选择2010年8月~2012年8月我院收治的中晚期宫颈癌患者75例,根据不同治疗方案将其分为单纯放疗组25例(单纯采用放疗治疗)、小剂量动脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在20 mg·m-2)及标准剂量静脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在40 mg·m-2)。观察并比较三组患者的临床疗效、两年生存率及毒性反应发生情况等。结果:小剂量动脉化疗组与标准剂量静脉化疗组的总有效率及两年生存率显著高于单纯放疗组(P0.05),小剂量动脉化疗组的总有效率和两年生存率高于标准剂量静脉组,差异具有统计学意义(P0.05)。单纯放疗组及小剂量动脉化疗组的毒性反应发生率显著低于标准剂量静脉组(P0.05);单纯放疗组与小剂量动脉化疗组患者的毒性反应发生率对比无统计学差异(P0.05)。结论:小剂量顺铂动脉化疗可以有效降低中晚期宫颈癌患者的急性毒性反应,值得临床进一步推广应用。     

化疗损伤性卵巢功能早衰小鼠动物模型的研究

目的探索建立化疗损伤性卵巢功能早衰动物模型的适宜方法及最佳时间。方法以70只ICR雌性小鼠为研究对象,腹腔连续注射顺铂7~14 d,观察不同剂量和时间条件下顺铂对小鼠的体重、卵巢功能、肝肾毒性及卵巢组织抗氧化系统各指标的变化。结果顺铂可引起小鼠体重明显下降,卵巢功能减退,出现肝肾毒性,并可引起卵巢抗氧化及氧化损伤指标的异常,与对照组比较均有明显差异。结论3.0~4.0 mg/(kg.bw)的顺铂作用7 d后即可引起小鼠出现明显的卵巢功能衰退、肝肾损伤,氧化损伤是顺铂产生其毒性作用的可能机制之一。该模型的生殖内分泌和病理组织学变化,与人类化疗损伤性卵巢功能早衰病变过程相似。     

奈达铂的临床应用新进展

奈达铂是铂类第二代抗肿瘤药物,临床研究表明奈达铂对大部分实体瘤,如头颈部肿瘤、食管癌、肺癌、卵巢上皮癌和宫颈癌等有效,其可联合多种化疗药物并具有放疗增敏作用。并可作为新辅助化疗应用在癌症术前治疗中。奈达铂的抗肿瘤作用优于顺铂,并且毒性谱有差异。主要不良反应如恶心呕吐发生率明显低于顺铂,联合放疗治疗中晚期癌症能提高有效率及生存率,明显减轻不良。值得临床进一步推广。依据NDP的临床前研究及临床应用,本文就奈达铂在临床上的应用作一简要综述。     

奈达铂的临床应用新进展

奈达铂是铂类第二代抗肿瘤药物,临床研究表明奈达铂对大部分实体瘤,如头颈部肿瘤、食管癌、肺癌、卵巢上皮癌和宫颈癌等有效,其可联合多种化疗药物并具有放疗增敏作用。并可作为新辅助化疗应用在癌症术前治疗中。奈达铂的抗肿瘤作用优于顺铂,并且毒性谱有差异。主要不良反应如恶心呕吐发生率明显低于顺铂,联合放疗治疗中晚期癌症能提高有效率及生存率,明显减轻不良。值得临床进一步推广。依据NDP的临床前研究及临床应用,本文就奈达铂在临床上的应用作一简要综述。     

富含miR-30a的牛初乳组分通过抑制癌细胞自噬促进顺铂化疗的肿瘤消亡

本实验首次发现牛初乳中富含miR-30a.取牛初乳中富含miR-30a的组分处理用顺铂化疗的癌细胞,能显著地抑制癌细胞自噬,促进癌细胞凋亡:单独使用顺铂化疗18 h的癌细胞凋亡率为12.5%,而化疗的同时施加富含miR-30a的牛初乳组分18 h后癌细胞凋亡率为56.5%.用这种富含miR-30a的牛初乳组分饲喂顺铂化疗的荷瘤小鼠,能更有效地抑制肿瘤生长:化疗小鼠饲喂牛初乳组分后,肿瘤直径自6 mm缩小为4.5 mm,而单独用顺铂化疗的肿瘤直径约8 mm.因此富含miR-30a的牛初乳组分能增进化疗药物的疗效.施用牛初乳组分,还可减少化疗药物的用量:单独用顺铂处理细胞18 h需20 mg/L剂量,加牛初乳组分后10 mg/L即可取得明显凋亡效果;单独用顺铂化疗荷瘤小鼠10天每次需500μg,而添加富含miR-30a的牛初乳组分后,顺铂剂量减半即可明显缩小肿瘤.     

Optimal controls for a model with pharmacokinetics maximizing bone marrow in cancer chemotherapy

A mathematical model for the depletion of bone marrow under cancer chemotherapy is analyzed as an optimal control problem. The control represents the drug dosage of a single chemotherapeutic agent and pharmacokinetic equations which model its plasma concentration are included. The drug dosages enter the objective linearly. It is shown that optimal controls are bang-bang, i.e. alternate the drug dosages at full dose with rest-periods in between, and that singular controls which correspond to treatment schedules with varying dosages at less than maximum rate are not optimal. Numerical simulations are given to illustrate the effect of the pharmacokinetic equations on the dosages.     

Mathematical approach to modeling of the treatment of suppurative processes

Consideration of an inflammation focus as an "open system" provided analogy between microbiological processes in inflamed wounds and in systems of continuous cultivation of microorganisms. Mathematical modeling of such systems is widely used. Some of the methods for the mathematical modeling were applied to chemoprophylaxis and chemotherapy of postoperative wounds. In modeling continuous cultivation of microorganisms it is usually necessary to determine optimal conditions for the maximum yield of their biomass. In modeling of wound treatment the aim was to determine the process parameters providing the minimum biomass. The described simple models showed that there could be certain optimal flow rate of the washing fluid in the aspiration-washing procedure for wound treatment at which the drug was not completely washed out while the growth rate of the microbial population was minimal. Such mathematical models were shown valuable in optimizing the use of bactericidal and bacteriostatic antibiotics.     

Mathematical model for chemotherapeutic drug efficacy in arresting tumour growth based on the cancer stem cell hypothesis

OBJECTIVE: Cancer stem cells have been identified as the growth root for various malignant tumours and are thought to be responsible for cancer recurrence following treatment. MATERIALS AND METHODS: Here, a predictive mathematical model for the cancer stem cell hypothesis is used to understand tumour responses to chemotherapeutic drugs and judge the efficacy of treatments in arresting tumour growth. The impact of varying drug efficacies on different abnormal cell populations is investigated through the kinetics associated with their decline in response to therapy. RESULTS AND CONCLUSIONS: The model predicts the clinically established 'dandelion phenomenon' and suggests that the best response to chemotherapy occurs when a drug targets abnormal stem cells. We compare continuous and periodic drug infusion. For the latter, we examine the relative importance of the drug cell-kill rate and the mean time between successive therapies, to identify the key attributes for successful treatment.     

Optimal control problems arising in cell-cycle-specific cancer chemotherapy

We explore mathematical properties of models of cancer chemotherapy including cell-cycle dependence. Using the mathematical methods of control theory, we demonstrate two assertions of interest for the biomedical community: 1 Periodic chemotherapy protocols are close to the optimum for a wide class of models and have additional favourable properties. 2 Two possible approaches, (a) to minimize the final count of malignant cells and the cumulative effect of the drug on normal cells, or (b) to maximize the final count of normal cells and the cumulative effect of the drug on malignant cells, lead to similar principles of optimization. From the mathematical viewpoint, the paper provides a catalogue of simplest mathematical models of cell-cycle dependent chemotherapy. They can be classified based on the number of compartments and types of drug action modelled. In all these models the optimal controls are complicated by the singular and periodic trajectories and multiple solutions. However, efficient numerical methods have been developed. In simpler cases, it is also possible to provide an exhaustive classification of solutions. We also discuss developments in estimation of cell cycle parameters and cell-cycle dependent drug action.     

DIFFERENCES AND SIMILARITIES IN ADJUVANT CHEMOTHERAPY IN MOUSE AND MAN

The effectiveness of adjuvant chemotherapy is easily demonstrated in many mouse models, whereas in man the response is good but far less spectacular. With the aid of a mathematical model the following variables in which differences may exist between mouse and man were tested: 1. Uniformity of tumour load in population 2. Cell kinetic factors in drug sensitivity 3. Variation of drug sensitivity among tumours 4. Drug penetration into tumour 5. Tumour antigenicity 6. Variation in growth rate among tumours It is concluded that factors 1 and 3 are responsible for the difference. Mouse models are more sensitive by selection of an effective drug and an optimal tumour load. Other factors seem not to affect the results.     

A mathematical model of doxorubicin penetration through multicellular layers

Inadequate drug delivery to tumours is now recognised as a key factor that limits the efficacy of anticancer drugs. Extravasation and penetration of therapeutic agents through avascular tissue are critically important processes if sufficient drug is to be delivered to be therapeutic. The purpose of this study is to develop an in silico model that will simulate the transport of the clinically used cytotoxic drug doxorubicin across multicell layers (MCLs) in vitro. Three cell lines were employed: DLD1 (human colon carcinoma), MCF7 (human breast carcinoma) and NCI/ADR-Res (doxorubicin resistant and P-glycoprotein [Pgp] overexpressing ovarian cell line). Cells were cultured on transwell culture inserts to various thicknesses and doxorubicin at various concentrations (100 or 50 μM) was added to the top chamber. The concentration of drug appearing in the bottom chamber was determined as a function of time by HPLC-MS/MS. The rate of drug penetration was inversely proportional to the thickness of the MCL. The rate and extent of doxorubicin penetration was no different in the presence of NCI/ADR-Res cells expressing Pgp compared to MCF7 cells. A mathematical model based upon the premise that the transport of doxorubicin across cell membrane bilayers occurs by a passive “flip-flop” mechanism of the drug between two membrane leaflets was constructed. The mathematical model treats the transwell apparatus as a series of compartments and the MCL is treated as a series of cell layers, separated by small intercellular spaces. This model demonstrates good agreement between predicted and actual drug penetration in vitro and may be applied to the prediction of drug transport in vivo, potentially becoming a useful tool in the study of optimal chemotherapy regimes.     

不同给药途径的新辅助化疗在晚期上皮性卵巢癌的疗效观察

目的:探讨新辅助化疗中不同给药方式在晚期上皮性卵巢癌的临床疗效及意义。方法:选取132例初治上皮性卵巢癌患者,临床分期为Ⅲc一Ⅳ期。随机平均分为4组(A组:单纯紫杉醇静脉化疗B组:单纯卡铂腹腔灌注C组:紫杉醇静脉联合卡铂腹腔D组:直接手术)。A、B、C三组给予1个疗程新辅助化疗后评估其疗效,行卵巢癌肿瘤细胞减灭术;D组直接手术治疗,比较各组治疗情况。结果:4组的满意肿瘤减灭率分别为78.8%、75.7%、87.9%、63.6%;化疗A、B与C组间、化疗各组与D组间在减灭术成功率、手术时间、术中出血量、术后排气时间上比较均有统计学意义(P0.05);新辅助化疗各组不良反应可耐受,均顺利完成手术,其中骨髓抑制及神经毒性以C组发生率较高(P0.01)。结论:1新辅助化疗可降低手术风险,有效提高满意的减灭术的成功率,改善生存质量。2静脉联合腹腔灌注较单途径用药的临床疗效好,毒副作用略高但可耐受。     

Comparison of the lateral tail vein and the retro-orbital venous sinus as routes of intravenous drug delivery in a transgenic mouse model

In mice, intravenous injections are commonly administered in the lateral tail vein. This technique is sometimes difficult to carry out and may cause stress to mice. Though injection through the retro-orbital venous sinus can provide certain advantages over lateral tail vein injection, this method is poorly defined and infrequently used. To compare the efficacy of these two routes of drug delivery, the authors injected MAFIA transgenic mice with the depletion agent AP20187, which selectively induces apoptosis in macrophages. Each mouse received five consecutive daily injections through either the lateral tail vein or the retro-orbital venous sinus. The authors then compared macrophage depletion in different tissues (lung, spleen, bone marrow and peritoneal exudate cells). Both routes of injection were similarly effective. A separate experiment using BALB/c mice indicated that retro-orbital venous sinus injection was the less stressful of the two methods.     

Ammonia absorption from the rumen to the systemic circulation with urea poisoning in goats.

To confirm the transfer of ammonia leaking from the rumen content via the liver to the perid by laparotomy. When ammonia leakage from the hepatic vein occurred, it was followed by an increase in ammonia concentration in the jugular vein. There were increases of ammonia concentration in the intestinal vein and in the thoracic duct after urea drenching. These increases suggested neither trapping ammonia in the peritoneal fluid nor responsibility for increases of ammonia in the systemic circulation, respectively. At times when respiration ceased due to urea poisoning, the peritoneal fluids wee in the fluid. The hypothesis of the peritoneal cavity-thoracic duct route of ammonia absorption, presented by some of previous workers on urea toxicity, was not supported in the present study.     

改良颈静脉置管术在自身给药成瘾模型优化中的作用研究

目的:探讨技术和方法的改进,提高动物颈静脉置管以及药物成瘾自身给药模型构建的成功率,为成瘾研究提供更稳定和高效的建模方法。方法:对建立自身给药模型的传统颈静脉置管术进行改良,选取成年雄性SD大鼠60只,按照随机数字表法分为传统手术组(n=30)和改良手术组(n=30),分别完成颈静脉置管术后,按照随机数字表法,再将每组分为对照训练组(n=15)和成瘾训练组(n=15),构建大鼠自身给药模型,观察两组大鼠自身给药模型成功率。结果:大鼠的颈静脉置管手术可能出现的手术并发症主要包括堵管、漏管、感染甚至死亡等,最主要的并发症是漏管,占比最大。颈静脉置管传统手术组手术成功率为43.33%±3.333,颈静脉置管改良手术组手术成功率为90.00%±3.333,显著高于颈静脉置管传统手术组(P0.05)。两组成瘾训练组有效鼻触次数均分别明显高于其对照训练组(P0.05)。结论:大鼠改良后的颈静脉置管手术效果明显优于传统手术,颈静脉置管手术成功率明显提高。