Schamhart D H, de Boer E C, Bevers R F, Kurth K H, Steerenberg P A
Department of Urology, University of Amsterdam, The Netherlands.
Prog Clin Biol Res. 1992;378:75-80.
The importance of adherence of BCG (Bacillus Calmette Guerin) to the bladder wall as an initiator of the processes leading to the BCG-induced antitumor activity is still controversial. A study was initiated addressing this subject by an experimental procedure modulating BCG adherence using pretreatment with pentosan polysulphate (PPS), a polysulphated polysaccharide with glycosaminoglycan (GAG)-like properties and reported bacterial antiadherence properties to the bladder mucosa. Furthermore, PPS is applied as a drug to treat chronic and radiation induced cystitis. It was reasoned that application of PPS during BCG treatment may prevent cystitis, a common side effect. However, nothing is known about a potential interaction of PPS with the effectiveness of BCG treatment. The results obtained with guinea pigs receiving prior to each of the 6 weekly instillation with BCG-RIVM (1 x E7 cfu) an intravesical pretreatment with 10 mg PPS in 1 ml for 0.5 hours indicated an enhancement of the PPD skin reaction, inflammatory response and number of iliac lymph nodes cells after instillation 6 compared to non-pretreated animals. These results, contrary to the expected, were supported by the indication of an increased binding of [3H]uracil-labeled BCG to the bladder after PPS pretreatment. To explain these results, the binding of PPS to the bladder wall and BCG were quantitated spectrophotometrically with DMB (dimethylmethylene blue). After administration of 40 g, 80 g, and 10 mg in appropriate volumes into the rat, guinea pig & human bladder 0.9 +/- 0.3, 4.3 +/- 1.1g, and 5.7 +/- 1.8 mg PPS (n > 5) were recovered respectively, showing a strong adherence.(ABSTRACT TRUNCATED AT 250 WORDS)
卡介苗(Bacillus Calmette Guerin,BCG)黏附于膀胱壁作为引发BCG诱导的抗肿瘤活性过程的起始因素,其重要性仍存在争议。一项研究通过实验程序来探讨这一主题,该程序使用戊聚糖多硫酸盐(PPS)进行预处理以调节BCG的黏附,PPS是一种具有糖胺聚糖(GAG)样特性的多硫酸化多糖,且有报道称其具有对膀胱黏膜的细菌抗黏附特性。此外,PPS被用作治疗慢性和放射性膀胱炎的药物。据推测,在BCG治疗期间应用PPS可能预防膀胱炎这一常见副作用。然而,关于PPS与BCG治疗效果之间的潜在相互作用尚无了解。对豚鼠在每周6次膀胱内灌注BCG-RIVM(1×10⁷cfu)之前,每次用10mg PPS于1ml中进行0.5小时的膀胱内预处理,结果显示与未预处理的动物相比,灌注6次后PPD皮肤反应、炎症反应及髂淋巴结细胞数量均增强。与预期相反,这些结果得到了PPS预处理后[³H]尿嘧啶标记的BCG与膀胱结合增加的证据支持。为解释这些结果,用二甲基亚甲基蓝(DMB)分光光度法定量测定PPS与膀胱壁及BCG的结合。分别向大鼠、豚鼠和人膀胱中以适当体积给予40μg、80μg和10mg PPS后,分别回收了0.9±0.3μg、4.3±1.1μg和5.7±1.8mg PPS(n>5),显示出强黏附性。(摘要截断于250字)