电针对去势大鼠外周血淋巴细胞雌激素受体影响的研究

目的　从生殖内分泌 -免疫网络角度探讨电针治疗围绝经期综合征的作用机制。方法　以去势大鼠为实验对象 ,取双侧三阴交、太溪、后三里穴 ,采用放射免疫法和流式细胞分析技术 ,观察电针治疗对去势大鼠血清雌激素 (E2 )、促黄体生成素 (LH)、促卵泡生成素(FSH)及外周血淋巴细胞内雌激素受体 (ER)水平的影响。结果　电针可使去势大鼠血清E2 明显升高 ,LH及FSH明显下降 ,外周血淋巴细胞内ER明显升高 ,与造模组比较有显著性差异。结论　电针可明显改善去势大鼠的生殖内分泌功能 ,并能调节免疫细胞的雌激素受体表达。     

过氧化氢对豚鼠耳蜗功能及形态的影响

目的 在体观察过氧化氢(H2O2)对豚鼠耳蜗功能及形态的影响。方法 实验动物分为4组，分别灌流人工外淋巴液(artificial perilymph,APL)，50μMH2O2，100μMH2O2和200μMH2O2(H2O2均溶于APL中)，并用Pl和H033342双染色方法观察H2O2引起的内耳细胞损伤情况。结果 所有H2O2灌流组复合动作电位((CAP)阈移和耳蜗微音电位(CM)幅度变化与人工外淋巴液组比较差异有显著性，且各H2O2组的变化呈现出浓度依赖性；Pl和H033342双染色方法发现外毛细胞是H2O2攻击的主要靶细胞，而Hensen细胞未见任何损伤痕迹。结论 H2O2可导致耳蜗功能下降及耳蜗毛细胞损伤：Hensen细胞较毛细胞可能具有更强的抗氧化能力。     

磁导向载体阿霉素介入治疗原发性肝癌的临床研究

目的：观察磁导向载体阿霉素(MTC-DOX)肝动脉介入治疗原发性肝癌的有效性和安全性。方法：将Seldinger导管超选择插入肿瘤供血肝动脉，以脉冲给药的方式注入MTC-DOX，21天为一周期，连续用药2周期以上按照WHO标准进行评价。结果：不能手术的原发性肝癌患共11例入组，10例可以评价疗效，治疗后NC7例，PD3例，中位肿瘤进展时间(TTP)为182天，有3例临床症状减轻，有4例生活质量改善，1年生存率达到54．5％；11例可以评价毒性，毒副反应均较轻，主要为轻中度的肝区疼痛和发热，少数患有胃肠道反应和一过性转氨酶升高。结论：采用磁导向载体阿霉素介入治疗原发性肝癌靶向性特别好，疗效明显，同时毒性反应轻微，值得进一步研究。     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

红细胞在抗肿瘤治疗中的作用

红细胞不仅可以运送氧、二氧化碳和清除循环免疫复合物，还能够识别、黏附、提呈肿瘤抗原，此外红细胞能够促进免疫细胞吞噬和杀伤肿瘤细胞的能力，因此红细胞在机体抗肿瘤免疫发挥重要作用。近年来，红细胞也可以开发作为药物载体治疗肿瘤，这与红细胞自身具有生物相容性和半透膜的特性有关。药物可以倍助渗透压梯度的不同、抗生素提高膜通透性，膜受体介导连接，以及交联介导连接等方法载入。已载入红细胞的药物半衰期延长，缓慢释放，受体液中酶等具有生物活性的物质降解，并且可以减轻药物毒副作用。缺点在于其靶向性单一。     

C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma.

PURPOSE: C-Jun NH(2)-terminal kinase (JNK) has been implicated in numerous functions including stress responses, apoptosis,and transformation. The role in transformation is based largely on studies of isolated cell types with little indication of whether JNK plays a general role in a specific human tumor type or whether this occurs in vivo. EXPERIMENTAL DESIGN: We examined 9 human prostate carcinoma cell lines in vitro and a representative line in vivo. RESULTS: For all of the cell lines proliferation is highly correlated with serum-supported JNK activity (r(Pearson) = 0.91; P = 0.004), whereas no relationship was observed for 10 human breast cancer cell lines (r(Pearson) = -0.32). Treatment with characterized antisense oligonucleotides complementary to sequences common to either the JNK1 or JNK2 family of isoforms showed that, whereas antisense JNK1 inhibited growth by a maximum of 57%, antisense JNK2 inhibited proliferation up to 80%. Sense and scrambled control oligonucleotides had little effect (average 3.7 +/- 1.5%). Moreover, systemic treatment of mice bearing established xenografts of PC3 prostate carcinoma cells with antisense JNK1 and JNK2 led to inhibition tumor growth by 57% (P < 0.002) and 80% (P < 0.001), respectively. The difference is significant (P < 0.012). Combined antisense treatment led to a significant increase in frequency of tumor regression (P = 0.022). CONCLUSION: These results indicate that JNK is required for growth of prostate carcinoma cells in vitro and in vivo, and additionally indicate that JNK2 plays a dominant role. The JNK pathway is a novel target in the treatment of prostate carcinoma.     

木犀草素对博莱霉素引起的大鼠肺纤维化模型的治疗作用

目的:研究木犀草素对大鼠肺纤维化的治疗作用。方法:观察不同剂量的木犀草素对博莱霉素诱导的大鼠肺纤维化肺组织的肺重量指数、丙二醛(MDA)、羟脯氨酸(HYP)含量及组织学变化的影响。结果:木犀草素在20,40和80mg·kg~(-1)剂量下连续灌胃给药21d,对模型大鼠的上述指标有不同程度的抑制作用,对其组织形态也有明显改善,且呈剂量效应关系。结论:木犀草素对大鼠肺纤维化模型具有较好的治疗效果。     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)