A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer.

BACKGROUND: Capecitabine (Xeloda) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients. PATIENTS AND METHODS: Forty-four patients received capecitabine 1250 mg/m2 twice daily (2500 mg/m2/day) for 14 days followed by 7 days of rest, for up to six cycles. RESULTS: Capecitabine produced an objective response rate of 34% (all partial responses) and stable disease in 14 patients (30%). The median time to disease progression (TTP) was 3.2 months [95% confidence interval (CI) 2.7-6.4 months] and median overall survival was 9.5 months (95% CI 6.9-13.2 months). Hand-foot syndrome (HFS), nausea, anorexia, diarrhea and vomiting were the most common adverse events. While HFS was the most frequent grade 3/4 toxicity (National Cancer Institute Common Toxicity Criteria), only 9% of patients experienced grade 3 HFS. Severe myelosuppression was not reported during the study. CONCLUSIONS: Capecitabine monotherapy is active and well tolerated as first-line therapy in patients with advanced/metastatic gastric cancer. Larger comparative trials investigating capecitabine-based combination regimens in patients with advanced gastric cancer are warranted.     

Arsenic trioxide induces selective tumour vascular damage via oxidative stress and increases thermosensitivity of tumours.

It has previously been found that the anti-leukaemia agent Arsenic Trioxide (ATO) causes vascular shutdown in solid tumours and markedly sensitizes tumours to hyperthermia. The present study was designed to evaluate the mechanism of action and dose-dependence of ATO-induced thermosensitization in FSaII and SCK murine tumours. The role of oxidative stress was studied by observing ATO-induced vascular shutdown in vivo and ATO-induced endothelial cell adhesion molecule expression in vitro in the presence or absence of an anti-oxidant. It was found that a dose as low as 2 mg/kg ATO impaired vascular function, as estimated by 86Rb uptake, in the tumour. The degree of tumour growth delay induced by 1 h of hyperthermia at 42.5 degrees C, applied 2 h after ATO injection, was proportional to the dose of ATO administered. In addition, it was found that ATO can directly thermosensitize tumour cells in vitro. The development of massive tissue necrosis in the tumour was observed in the days after treatment, especially with the combination of ATO and heating. ATO-induced adhesion molecule expression in vitro was abolished when the anti-oxidant n-acetyl-cysteine (NAC) was introduced prior to exposure, while the addition of NAC in vivo partially blocked ATO-induced vascular shutdown. These results suggest that the expression of adhesion molecules by the vasculature due to oxidative stress contribute to the ATO-induced selective tumour vascular effects observed and that the clinical use of ATO to increase tumour thermosensitivity via direct cellular and vascular effects appears feasible.     

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.     

妊高征孕妇血浆硒水平与红细胞内谷胱甘肽过氧化物酶的关系

目的 探讨妊高征孕妇血浆中硒浓度与红细胞内谷胱甘肽过氧化物酶的关系.方法 应用原子吸收法及细胞化学发光检测法测定49例妊高征孕妇(妊高征组)和34例正常孕妇(正常妊娠组)血浆中硒的水平及红细胞内谷胱甘肽过氧化物酶(GSH-PX)的浓度.结果 妊高征组血浆硒水平及红细胞内GSH-PX浓度明显低于正常妊娠组,而且孕妇血浆中硒水平与红细胞内GSH-PX浓度之间呈直线回归关系,即随着血浆硒水平的升高,红细胞内GSH-PX也升高.结论 孕妇血浆硒水平与红细胞内GSH-PX浓度与妊高征的发病有一定的关系.     

Pulmonary tuberculosis in five young infants with nursery exposure: clinical, radiographic and CT findings

Clinical, radiographic (n = 5) and CT findings (n = 4) of five Korean infants ranging in age from 2 to 3 months with confirmed tuberculosis were retrospectively analysed. All of the patients were symptomatic, anergic to tuberculin, and had a positive culture of Myobacterium tuberculosis in gastric aspirates. The probable source of infection was the hospital in which they were born. CT scans demonstrated hilar and mediastinal lymph node enlargement with central low attenuation and peripheral enhancement in all cases. CT may be useful in diagnosis by demonstrating characteristic adenopathy and disseminated disease in young infants. Received: 2 September 1997 Accepted: 23 April 1998     

自体心包瓣“内皮化”的实验研究

目的 探讨有利于自体心包瓣内皮化的处理方法。方法 将体外培养小牛主动脉内皮细胞接种于不同方法处理的自体牛心包表面。采用＾３Ｈ－ＴｄＲ摄取量测定、扫描电镜及放射免疫法观察不同处理方法对接种后内皮细胞生长、前列环素（ＰＧＩ２）合成量和细胞内ｃＡＭＰ含量的影响。结果 三种不同浓度戊二醛短时间（１０ｍｉｎ）处理的心包表面内皮细胞均可生长,其中以体积分数为０．２％戊二种不同浓度戊二醛短时间（１０ｍｉｎ）处理     

双特异性抗体治疗肿瘤的可行性研究

肽图分析是验证rhIL-2的重要手段之一.rhIL-2具有133个氨基酸,在其一级结构的序列中有四个甲硫氨酸切点,可用化学裂解的方法将甲硫氨酸肽键打开,进行肽谱分析,以对其进行验证.为了有效地对甲硫氨酸进行裂解,我们用70%甲酸溶解CNBr~2,保持CNBr的高浓度小体积,使rhIL-2在1.5mlEppedorf管中,室温条件下有效地打开甲硫氨酸肽键.同时比较了CNBr浓度、裂解时间以及在不同浓度的梯度胶中作SDS-PAGE对实验结果的影响,确定了最佳的实验条件,获得了良好的实验结果.本文虽以rhIL-2为例,但对所有带甲硫氨酸的细胞因子均可用本方法进行肽图分析.