d-宁烯、丹参及姜黄素衍生物对ras基因产物膜结合和细胞间隙信息传导的影响

目的旨在寻找新型抗肿瘤药物,进一步研究d-宁烯、丹参及姜黄素衍生物的抗肿瘤机理。采用分子生物学方法及划痕标记染料示踪技术,研究了4种人实体瘤起源的细胞系的细胞间隙信息传导(GJIC)、H-ras癌基因表达以及ras癌基因产物(P21^ras蛋白)表达状态,并观察了4种天然产物对它们的影响。结果表明,细胞内染料传输功能的丧失与ras基因突变率呈正相关;单萜化合物d-宁烯和酚类化合物丹参衍生物的抗肿瘤作用可能与抑制P21^ras蛋白膜结合和增强细胞间隙信息传导功能有关。提示Ras癌基因产物P21^ras蛋白膜结合的抑制与细胞间隙信息传导功能的增强有直接关系。     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.     

Expression of c-erbB-2 protein in keratinocytes of oral mucosal lichen planus and subsequent squamous cell carcinoma

Oral mucosal lichen planus (OMLP) is a well recognized mucosal disease with unknown etiology. Considerable controversy exists as to whether OMLP is intrinsically premalignant, or if the disorder facilitates the development of oral mucosal squamous cell carcinoma (OMSCC) by external factors. The aim of the present study was to investigate the expression of c-erbB-2 protein in the keratinocytes of initial biopsies of oral mucosal disorders diagnosed as OMLP with no evidence of epithelial dysplasia. and to compare the results with the expression of c-erbB-2 protein in subsequent biopsies obtained from the same patients. These results were compared with the findings from control groups (patients with dysplasia with no evidence of OMLP, patients with OMSCC with no evidence of OMLP and normal oral mucosa). The expression of the c-erbB-2 protein was evaluated by immunohistochemical staining of the gene product with the avidin-biotin-complex method using paraffin-embedded tissue sections. Five of the initial biopsies from patients with OMLP expressed the c-erhB-2 protein and one did not. None of the OMLP cases that subsequently showed evidence of dysplasia expressed the c-erhB-2 protein, and of the three OMSCC specimens from the patients with OMLP. two were negative and one expressed c-erbB-2 protein. The specimens from the control groups all expressed the c-erhB-2 protein. The results indicated the probability of the absence of c-erbB-2 staining being an indication of a potential for neoplastic transformation in OMLP with dysplastic changes.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996     

西安市城市居民食管癌的病因研究:烟酒因素的作用

本文报道了1984年10月~1985年10月西安市城市居民138例食管癌的病例对照研究。结果表明,吸烟为食管癌发病的危险因素,OR_M-H为4.12(95% CI为1.57~6.54)。OR与吸烟量、吸烟年限有显著剂量效应关系。吸烟作为食管癌的可能致病因子其潜隐期为37.19年。饮酒与食管癌的联系不显著(χ²=1.03,P﹥0.05)。作者认为吸烟单独或与其它因素共同作用下可能参与食管的癌变过程。     

脐血CD34~+细胞体外短期培养扩增研究

为寻找更有效的体外扩增脐血CD34 + 细胞的造血细胞因子组合 ,采集健康产妇脐带血 ,用免疫磁珠法分选CD34 + 细胞。采用SCF、FLT3 L、TPO和IL 34种具有早期作用的细胞因子的不同组合进行脐血CD34 + 细胞短期无血清液体培养 ,观察培养前后有核细胞、CD34 + 细胞、CD34 + /CD38- 细胞、CFU GEMM、CFU GM和BFU E数量的变化。结果在 3种不同的细胞因子组合中 ,同时应用SCF、FLT3 L、TPO和IL 34种细胞因子培养 7d的扩增效果最好。突出的发现是在这种条件下CD34 + /CD38- 细胞亚群达到平均 1 97.9倍的扩增效果。提示 :SCF、FLT3 L、TPO和IL 34种细胞因子是脐血CD34 + 细胞体外扩增理想的细胞因子组合     

酸性成纤维细胞生长因子的分离纯化及活性鉴定

目的：从牛脑中分离纯化酸性成纤维细胞生长因子（aFGF)并鉴定生物活性，方法：根据DenisGOSPODAROW-ICZ的方法，新鲜牛脑匀浆，三步硫酸铵盐析。最后沉淀物溶解透析后予离子交换层析及琼脂糖胶亲和层析，促3T3细胞DNA合成率鉴定生物活性。结果：用1.0mol/LNaCl的缓冲液洗脱得到分子量为13600的多肽，得率为610μg/kg牛脑，氨基酸组成分析与已知的aFGF相同，促3T3细胞DNA合成的最低浓度为0.5ng/ml，最大效应浓度50ng/ml，ED50值为8ng/ml。结论：aFGF具有强烈的促细胞增殖作用。     

P53、P16、Bcl-2基因及产物在原发性肺癌中的表达及其临床病理意义

目的 :探讨原发性肺癌 Mtp5 3、p16、Bcl- 2的异常表达与肺癌发生、发展的关系 ,以及它们之间的调控关系。 方法 :用免疫组化技术检测 (L SAB) 114例原发性肺癌组织中 p5 3、p16、Bcl- 2的表达。并用 PCR技术对 6 2例 p16蛋白丢失的肺癌组织中 p16外显子 2 (p16 E2 )的缺失进行分析。 结果:p5 3蛋白异常表达与肺癌组织学类型、分化程度无关 (P >0 .0 5 ) ,但与淋巴结转移情况有关 (P >0 .0 5 )。 p16蛋白阳性表达率与肺癌的组织学类型无关 ,但是其表达水平与非小细胞肺癌 (NSCL C)的细胞分化程度和淋巴结转移密切相关 (P <0 .0 5 )。 NSCL C中 p16E2的缺失率为 45 .2 %,其缺失水平随淋巴结转移和组织学分级的升高而升高 (P <0 .0 5 )。 SCL C(小细胞肺癌 )和正常肺组织中无 p16 E2的缺失。 Bcl- 2在小细胞肺癌中阳性率 6 2 .2 %显著高于 Sq Ca(鳞癌 )的 2 5 %和 Ad Ca(腺癌 )的 9.1%(P <0 .0 5 ) ,与细胞分化程度和淋巴结转移情况无关。另外 ,p5 3与 p16蛋白之间存在调控关系。 结论 :(1) p16、p5 3、Bcl- 2的异常参与肺癌的发生、发展过程。 (2 ) p16基因及产物的异常表达与 NSCL C的组织学分级和淋巴结转移相关 ,可能参与 NSCL C的发生、发展和转移过程。 (3) Bcl- 2反映 SCL C的分之生物学行为和临床     

安体维康诱导肝细胞凋亡实验研究及临床观察

目的 :评价中药制剂安体维康 ( Antivirus Compound,ATVC)诱导人肝癌细胞凋亡的作用及临床疗效。方法 :采用 MTT(细胞毒 )实验培养人肝癌细胞株 BEL - 740 2细胞 ,加入不同浓度安体维康药液进行培养与对照组进行比较。临床给原发性肝癌 1 0例服用安体维康胶囊 3个月。结果 :安体维康能抑制人肝癌细胞株 BEL- 740 2细胞生长 ,有诱导肝细胞凋亡的作用。其作用强弱在一定程度上存在剂量和时间效应。服用安体维康的肝癌患者临床症状明显改善。结论 :安体维康可诱导人肝癌细胞调亡 ,对原发性肝癌有一定临床疗效