肺腺癌患者化疗前后血清可溶性Fas检测的临床意义

目的 检测肺腺癌患者化疗前后血清可溶性Fas(sFas)水平并探讨其临床意义.方法 应用酶联免疫吸附试验法(ELISA)检测60例肺腺癌患者化疗前后血清sFas水平,并同时检测30例正常人血清sFas水平作对比分析.结果 肺腺癌患者血清sFas水平明显高于正常对照组(P＜0.01).血清sFas水平与临床分期有关,与肺腺癌患者性别、年龄、细胞分化程度无关.Ⅳ期肺腺癌血清sFas水平明显高于Ⅲ期和Ⅱ期(P＜0.01),Ⅲ期明显高于Ⅱ期(P＜0.01).化疗后有效(完全缓解和部分缓解)患者血清sFas水平明显低于化疗前(P＜0.01).结论 血清sFas与肺腺癌的发生及发展有一定关系,检测血清sFas有可能成为肺腺癌辅助诊断、病情发展及化疗疗效观察的一项有价值的指标.     

血清IL-8和sApo-1/Fas与乳腺癌患者临床病理学参数的关系

目的:探讨外周血IL-8和sFas在不同绝经状态、不同雌激素受体状态(ER)、不同转移情况的乳腺癌术后复发及转移患者中的表达及其临床意义.方法:采用酶联免疫双抗体夹心法检测94例乳腺癌术后复发及转移患者和30例正常人的血清IL-8和sFas水平,并比较它们与绝经状态、ER状态、不同转移情况的关系以及化疗对其影响.结果:1)乳腺癌患者血清IL-8及sFas水平明显高于正常人(P＜0.05).2)血清IL-8与雌激素受体(ER)状态和骨转移关系密切:ER(-)者高于ER( )者(P＜0.05);有骨转移者高于局部复发及/或区域淋巴结转移(P＜0.01)以及肝、肺转移者(P＜0.05).3)血清sFas水平与绝经状态及肝、肺转移关系密切:绝经后患者高于绝经前患者(P＜0.05);有肝、肺转移者高于局部复发及/或区域淋巴结转移(P＜0.01)以及骨转移者(P＜0.05).4)化疗后血清sFas水平较化疗前下降(P＜0.05),而血清IL-8无明显变化.结论:血清IL-8和sFas水平与乳腺癌患者的生物学行为及预后有一定关系,值得进一步研究.     

恶性肿瘤患者血清CA125、CA242、CA153水平检测及临床意义

目的评价检测恶性肿瘤患者血清CA125、CA242、CA153水平的临床价值.方法用酶联免疫吸附法测定97例四种恶性肿瘤患者血清CA125、CA242、CA153的含量.结果肺癌患者血清CA125、CA242、CA153水平明显高于正常对照组(P＜0.01或P＜0.05),肺腺癌患者血清CA125水平明显高于肺鳞癌(P＜0.05),肺癌Ⅳ期患者血清三种肿瘤标志物含量明显高于Ⅲ期(P＜0.01或P＜0.05),宫颈癌和非何杰金氏淋巴瘤(NHL)患者血清CA125水平明显高于对照组(P＜0.01或P＜0.05),宫颈癌Ⅳ期血清CA125水平明显高于Ⅱ、Ⅲ期(P＜0.05),肺癌患者血清CA125水平明显高于鼻咽癌患者(P＜0.05).血清CA125敏感性高低依次是肺癌＞NHL＞宫颈癌＞鼻咽癌(P＜0.05).结论血清CA125 CA242、CA153水平检测对恶性肿瘤的诊断及分期有一定参考价值.     

CXCL9和碳酸酐酶Ⅸ在鼻咽癌患者血清中的表达及其临床意义

目的 研究鼻咽癌患者血清趋化因子(CXCL)9和碳酸酐酶Ⅸ(CAⅨ)水平与其临床病理因素的相关性.方法 选择鼻咽癌患者共32例,结果统计过程中因资料遗失脱落2例,实际完成30例;检测鼻咽癌组和对照组血清CX-CL9和CAⅨ水平;分析血清CXCL9和CAⅨ表达水平与患者的性别、年龄、肿瘤大小、TNM分期、病理类型及淋巴结转移等临床病理参数的相关性;所有患者均给予2年定期随访,比较死亡患者与存活患者血清CXCL9和CAⅨ水平.结果 鼻咽癌组较对照组血清CXCL9和CAⅨ水平均明显增高(P＜0.01);血清CXCL9和CAⅨ表达水平与鼻咽癌患者的性别、年龄、大小及病理类型无明显相关性(P＞0.05),而与鼻咽癌患者TNM分期、淋巴结转移呈明显相关(P＜0.叭).随访2年显示:6例死亡,24例存活;死亡患者入院时血清CXCL9和CAⅨ水平均明显高于存活者入院时(P＜0.01).结论 鼻咽癌患者血清CXCL9和CAⅨ的表达水平明显升高,与鼻咽癌的恶性程度呈显著性相关,可能是评估鼻咽癌患者预后的重要指标.     

高聚金葡素对放疗后鼻咽癌患者细胞免疫功能影响

目的:探索高聚金葡素(highly agglutinative staphylococcin HAS)对鼻咽癌(NPC)放疗后患者细胞免疫功能的影响.方法:34例放疗后获CR患者分成2组,A组(治疗组)17例接受HAS治疗;B组(对照组)17例仅予以一般治疗(复合维生素).检测两组治疗前后NK活性和CD4/CD8比值的变化.结果:A组治疗后NK活性和CD4/CD8值均明显提高(P＜0.01),B组无明显变化.结论:HAS可增强NPC放疗后患者的NK活性,对细胞亚群有调节作用.     

鼻咽癌患者血清sICAM-1和SAA1及HSP70检测临床意义分析

目的:探讨可溶性细胞间黏附分子-1(sICAM-1)、血清淀粉样蛋白A1 (SAA1)和热休克蛋白70 (HSP70)在鼻咽癌患者血清中的表达水平及其诊断价值.方法:用酶联免疫吸附法(ELISA)对30例鼻咽癌转移患者,27例鼻咽癌未转移患者和30名正常人的血清sICAM-1、SAA1和HSP70进行检测.结果:血清sICAM-1、SAA1和HSP70含量在鼻咽癌组与正常对照组、鼻咽癌淋巴结转移组与无淋巴结转移组之间差异均有统计学意义,P值均＜0.01.血清sICAM-1和HSP70水平在不同TNM分期中差异有统计学意义,随着TNM分期的提高,其血清水平逐步提高,P＜0.01.而且这3种蛋白质在鼻咽癌患者血清中均具有相关性,即在鼻咽癌患者血清中,这3种蛋白质中的某一种蛋白质含量升高,则另外2种蛋白质的含量也会上升,P＜0.01.结论:经双向电泳和质谱鉴定出的蛋白质在3组标本中确实具有差异,且有一定意义.sICAM-1和HSP70的表达随着鼻咽癌的发展逐渐增强,可能反映鼻咽癌的进展.动态检测鼻咽癌患者血清sICAM-1、SAA1和HSP70的水平,可作为鼻咽癌诊断的一个重要指标,有一定的临床价值.     

卵巢上皮性肿瘤患者血清层粘连蛋白检测的临床意义

目的:探讨卵巢上皮性肿瘤患者血清层粘连蛋白含量及临床意义.方法:应用放射免疫技术测定48例卵巢恶性上皮性肿瘤患者术前血清层粘连蛋白(LN)含量,并测定了其中43例患者术后血清LN含量.结果:卵巢恶性上皮性肿瘤组术前血清LN含量显著高于对照组及良性肿瘤组(P＜0.01),术后明显下降,手术前后血清LN含量差异有显著性意义(P＜0.05);卵巢恶性上皮性肿瘤患者低度分化组血清LN含量显著高于中度及高度分化组(P＜0.05),腹水阳性组LN含量显著高于腹水阴性组(P＜0.05),晚期患者血清LN含量明显高于早期患者(P＜0.05).结论:卵巢恶性上皮性肿瘤患者血清LN含量与肿瘤的浸润及转移过程密切相关;观察血清LN含量及其变化,对卵巢恶性上皮性肿瘤患者的病情及预后判断有重要的参考价值.     

外周血淋巴细胞亚群水平变化在鼻咽癌中的意义

目的 探究外周血淋巴细胞亚群水平变化在鼻咽癌(NPC)中的意义.方法 选取NPC患者60例为试验组,选取健康体检者30例为对照组.采用流式细胞仪检测试验组治疗前后和对照组的外周血中CD3+、CD4+、CD8+细胞亚群及自然杀伤细胞(NK)水平;采用免疫组化法和Western Blot检测试验组治疗前后肿瘤组织中白细胞介素-21(IL-21)蛋白表达水平.结果 治疗前,试验组外周血中CD3+、CD4+、CD4+/CD8+及NK细胞水平明显低于对照组(P﹤0.01),CD8+细胞水平明显高于对照组(P﹤0.01);治疗后,试验组外周血中CD4+、CD4+/CD8+和NK细胞水平均较本组治疗前明显上升(P﹤0.01),CD8+细胞水平较本组治疗前明显下降(P﹤0.01);治疗后,早期NPC患者的总缓解率高于晚期NPC患者(P﹤0.05);免疫组化法和Western Blot检测结果显示,治疗前,NPC患者肿瘤组织中IL-21蛋白的阳性表达率及表达水平均高于治疗后(P﹤0.05).结论 NPC患者外周血中淋巴细胞亚群及NK细胞的检测对鼻咽癌的早期诊断及疗效评判具有重要意义.     

急性白血病患者血清sFas表达

[目的]检测急性白血病患者血清sFas含量分析其在病情变化中的意义。[方法]应用流式细胞仪免疫荧光双标法检测70例急性白血病患者(难治复发组43例,缓解组27例)的血清sFas含量,并与正常对照组28例比较。[结果]难治复发组患者sFas含量(6.23±1.31)μg/L,显著高于正常对照组(4.85±0.92)μg/L和缓解组(5.12±1.08)μg/L,P<0.05。[结论]血清sFas水平与急性白血病病情变化有关。     

多发性骨髓瘤患者血浆可溶性Fas水平检测及其临床意义

目的探讨多发性骨髓瘤患者血浆可溶性Fas(sFas)水平变化及其临床意义.方法用酶联免疫吸附试验法(ELISA)检测28例多发性骨髓瘤患者及25例正常对照血浆sFas值,并与多发性骨髓瘤患者骨髓涂片中骨髓瘤细胞数作相关分析.同时测定其中6例多发性骨髓瘤患者化疗前后sFas水平.结果多发性骨髓瘤患者sFas水平显著高于正常对照组[(10.36±6.87)μg/L,vs(5.58±2.78)μg/L,P＜0.01].其中6例多发性骨髓瘤患者化疗前sFas水平显著高于化疗后完全缓解时(P＜0.01).此外,骨髓涂片中骨髓瘤细胞数高者(≥15%)sFas水平显著高于骨髓瘤细胞数低者(＜15%)[(13.86±7.10)μg/L,vs(6.36士3.34)μg/L,P＜0.01].结论提示血浆sFas 水平升高与多发性骨髓瘤的发生发展可能有关.     

Toxicology and pharmacokinetics of (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38)

Preclinical studies on toxicology and pharmacokinetics were performed for (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38) in rats and a dog after ld₁₀ and ld₅₀ assessment in mice. In drug-treated rats, ura and creatinine concentrations were 1,4-1.9 times those in control rats. Histopathology showed necrosis of tubular epithelium of the kidneys, which was comparable to damage observed after treatment with cisplatin (CDDP), and extensive necrosis of crypt epithelium, especially in the ileum.Similar to CDDP, TNO-38 was emetic in the dog. Non-specific subacute inflammatory changes were observed in the ileum. Renal damage was much less pronounced.Half-lives of distribution and elimination were 6.2 min and 5.2 days, respectively. The cumulative excretion of Pt in urine over 1 and 7 days after drug treatment was 38.3 and 49.3% of the dose, respectively. Twelve weeks after drug administration, Pt concentrations were highest in kidneys and liver.TNO-38 is adequately water soluble. Its reported antitumour activity is consistently lower than that of CDDP. The drug's toxicity was, in general, comparable to that of CDDP. Its pharmacokinetic profile was very similar to that of CDDP. It is concluded that TNO-38 should probably not be further evaluated in clinical studies.     

Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice.

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.     

Clinical trials of Herceptin(R) (trastuzumab)

This report summarises the clinical efficacy and safety findings from clinical trials of the new anti-HER2 monoclonal antibody Herceptin(R) (trastuzumab). Data from pivotal trials indicate that trastuzumab is active when added to chemotherapy in patients with advanced metastatic breast cancer. In particular, the combination significantly prolonged the median time to disease progression, increased the overall response rate, increased the duration of response, and improved median survival time by approximately 25% compared with chemotherapy alone. Furthermore, trastuzumab is active as a single agent in women with HER2-positive metastatic breast cancer, inducing durable objective tumour responses. In total, 15% of patients who had received extensive prior treatment for metastatic disease had an objective response. The median duration of response was 9.1 months following administration of single-agent trastuzumab. Notably, 2% of patients were free of disease progression at 6 months. The safety profile of trastuzumab either given alone or in combination was favourable.     

Synergism of cytotoxicity between cis-diaminedichloro-platinum-(ii) and cis-diamine(1,1-cyclobutanedicarboxylate)-platinum-(ii)

In an attempts to increase the antitumor effect and to reduce normal tissue toxicity, the combined cytotoxic effect of cis-Diamminedichloroplatinum (II) (CDDP) and cis-diammine(1,1-cyclobutane dicarboxylate) platinum (II) (CBDCA) was investigated using HeLa and colon 26 cell lines and the combination index (CI). Cytotoxicity of the combination of CDDP and CBDCA on 27 surgically resected specimens of human gastric and colorectal adenocarcinomas was also evaluated using the in vitro succinate dehydrogenase inhibition (SDI) test. The CI values varied with the dose ratio examined (1:1-1:6) of CDDP and CBDCA, with findings that CI<1, synergy, was obtained at fraction affected (Fa)>0.75 for HeLa cells and at Fa<0.9 for colon 26 cells in cases of a dose ratio of 1:1 to 1:2. Of all 27 clinical human adenocarcinomas, the succinate dehydrogenase (SD) activity was significantly lower in cancer cells concomitantly exposed to both CDDP and CBDCA than in those exposed to either drug alone. These positive effects of a combination of two platinum analogues on human malignant tissues have heretofore not been reported, which would warrant the clinical application of this combination for human malignant tumors.     

In vitro evaluation of dichloro-bis(pyrazole)palladium(II) and dichloro-bis(pyrazole)platinum(II) complexes as anticancer agents

Introduction  Cisplatin (cis-diamminedichloroplatinum) was first identified for its anti-bacterial activity, and was later also shown to be an efficient anticancer agent. However, the therapeutic use of this anticancer drug is somewhat limited by its toxic side effects, which include nephrotoxicity, nausea, and vomiting. Furthermore the development of drug-resistant tumours is commonly observed following therapy with cisplatin. Hence there is a need for improved platinum derived drugs to overcome these limitations. Aims  Apoptosis contributes significantly to the cytotoxic effects of anticancer agents such as cisplatin; therefore in this study the potential anticancer properties of a series of pyrazole palladium(II) and platinum(II) complexes, [(3,5-R₂pz)₂PdCl₂] {R = H (1), R = Me (2)} and [(3,5-R₂pz)₂PtCl₂] {R = H (3), R = Me (4)}, were evaluated by assessment of their pro-apoptotic activity. Methods  The induction of apoptosis was measured in CHO cells by the detection of phosphatidylserine (PS) exposure using the annexin V and APOPercentage™ assays; DNA fragmentation using the Terminal deoxynucleotide transferase dUTP Nick End Labelling (TUNEL) assay; and the detection of activated caspase-3. Results  The platinum complexes were shown to be considerably more active than the palladium complexes, with complex 3 demonstrating the highest level of cytotoxic and pro-apoptotic activity. The LD₅₀ values for complex 3 and cisplatin were 20 and 70 μM, respectively, demonstrating that the cytotoxic activity for complex 3 was three times higher than for cisplatin. Various human cancer cell lines, including CaSki, HeLa, as well as the p53 mutant Jurkat T cell line were also shown to be susceptible to complex 3. Conclusions  Collectively, this in vitro study provides insights into action of palladium and platinum complexes and demonstrates the potential use of these compounds, and in particular complex 3, in the development of new anticancer agents.