A new experimental trial using repeated heating every 24 hours for local hyperthermic therapy with bleomycinin vivo

This report presents the effect of repeated heating every 24 hrs using bleomycin (BLM) which, although seemingly contrary to the usual agreement that hyperthermia should be carried out with a long interval due to thermotolerance, holds many possibilities. FM3A cells on the foot pad of C3H mouse were immersed in a heated water bath at 43 and 44°C for 30 min. The effect of repeated heating was appreciated by an improved growth curve and 50 day survival compared to mice which received heating twice with a 96-hr interval. Repeated heating every 24 hrs 5 times with BLM suppressed tumor growth significantly as compared to heating twice with a 96-hr interval without BLM. The longest survival time was obtained by the repeated heating with BLM among all protocols. There is therefore a good possibility that more effective results could be obtained clinically by repeated heating over a short period.     

Palliative treatment of malignant ascites by intraperitoneal bleomycin after dialytic ultrafiltration with haemofilter

Dialytic ultrafiltration with haemofilter was performed in 16 patients with malignant ascites refractory to treatment with sodium restriction, diuretic and systemic chemotherapy. A continuous flow of ascitic fluid at a rate of 300–400 ml/min through a haemofilter was maintained by a blood pump. The protein-rich ascitic fluid was re-infused into the peritoneal cavity with sodium and water removed. An average of 5.2 1 of filtrate was removed over a mean interval of 3.5 h. Bleomycin (60 mg) was administered intraperitoneally following the procedure. Complete response was observed in six patients (37.25%) and partial response occurred in four (25%). The remaining patients showed no response. Complications of the dialytic ultrafiltration procedure and toxicity of intraperitoneal administration of bleomycin were minimal. The technique of dialytic ultrafiltration is simple, safe and cost-effective and could be used as an adjuvant therapy for intraperitoneal chemotherapy.     

Electrochemotherapy significantly inhibits the growth of colon 26 tumors in mice

Electrochemotherapy is a novel antitumor treatment involving the systemic administration of bleomycin followed by the delivery of electrical pulses to the tumor. The present study investigates the effects of electrochemotherapy on the growth of colon 26 cells inoculated subcutaneously into the backs of BALB/c mice. The mice were divided into the following four experimental groups: 20 that received no further treatment after the inoculation of colon 26 cells (control group); 20 that received 500 μg of bleomycin intraperitoneally 7 and 9 days after the inoculation (BLM group); 20 that received electric pulses to the tumor 7 and 9 days after the inoculation (EP group); and 30 that received electrochemotherapy 7 and 9 days after the inoculation (ECT group). During 28 days of observation, no deaths due to tumor progression occurred in the ECT group, but there were 18 in the control group, 11 in the BLM group, and 18 in the EP group. While weight loss was observed in all groups, it was most remarkable in the control group. Tumor growth was significantly inhibited in the ECT group, compared to the other experimental groups (P<0.01). The results of this study demonstrated that electrochemotherapy significantly inhibited the growth of colon 26 tumors in mice, without causing any remarkable adverse effects.     

益肺抗纤方对博莱霉素诱导大鼠肺纤维化的防治作用

目的 :观察益肺抗纤方抗肺纤维化的作用。方法 :实验用雄性Wistar大鼠分为 4组 ,对照组、模型组、益肺抗纤方组、地塞米松组 ;对照组气管内注入生理盐水 ,其余 3组气管内注入博莱霉素制作大鼠肺纤维化模型。造模后 ,益肺抗纤方组给益肺抗纤方 10ml/kg灌胃 ,地塞米松组给地塞米松 1.5mg/kg腹腔注射 ,模型组和对照组均给生理盐水灌胃 ,均给药 1次 /d。观察各组大鼠肺部病理变化 ,测定各组第 7d、2 8d肺组织超氧化物歧化酶(SOD)、脂质过氧化物 (LPO)和羟脯氨酸 (HP)的含量。结果 :气管内注入博莱霉素第 2 8d时 ,模型组多呈 3级肺纤维化和 1级肺泡炎改变 ;益肺抗纤方组多呈 1级纤维化改变 ,肺泡炎不明显 ;地塞米松组多呈 1级纤维化和 1～ 3级肺泡炎改变 ;对照组呈正常肺结构。第 2 8d时 ,模型组和地塞米松组肺组织SOD活性均较对照组明显下降 (P <0 .0 1和P <0 .0 5 ) ,地塞米松组较模型组SOD活性下降更明显 (P <0 .0 5 ) ;益肺抗纤方组与对照组之间SOD活性无明显差别。对照组、模型组、益肺抗纤方组肺组织LPO含量明显低于地塞米松组 (P <0 .0 1) ;益肺抗纤方组与对照组和模型组之间无明显差别。结论 :益肺抗纤方可通过提高SOD活性 ,降低脂质过氧化 ,减轻氧自由基损伤 ,抑制胶原沉积 ,保护肺组织     

平阳霉素治疗血管瘤、血管畸形后组织学观察

目的 :观察平阳霉素治疗血管瘤、血管畸形后引起的组织学变化。方法 :13例不同类型的血管病变 ,分1～ 3次注射平阳霉素 4～ 2 4mg ,多次注射者间隔 10～ 12d .在末次注射后 12～ 15d切除治疗后的病变组织进行组织学观察。结果 :注射 1次的标本中血管壁增厚 ,管腔变狭窄 ;注射 2次的标本中管腔闭塞 ,管壁失去正常结构 ;注射 3次的标本中管壁结构消失 ,组织纤维化。结论 :平阳霉素瘤腔内注射后可引起血管内膜变化 ,致使管腔闭塞 ,从而治愈血管瘤及血管畸形     

Intracerebral chemotherapy in the 9L rat brain tumor model

Summary We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5–2.5 mg/kg) nor multiple ip treatments (0.5–1.0 mg/kg × 5, q 6 h) were effective in prolonging the survival, single is dose AZQ (5–50 g/rat) treatment significantly increased the MST of the treated animals (P < 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Patinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.     

Vinorelbine, bleomycin and methotrexate as a salvage therapy for patients with head and neck squamous carcinoma in relapse after cisplatin/fluorouracil

Background: Cisplatin (CDDP) and 5-fluorouracil (5-FU) represent the standard chemotherapy for advanced/recurrent head and neck squamous carcinoma (HNSC); however, the duration of response is often short, with a median survival of only five to six months.Patients and methods: Patients with HNSC were treated with vinorelbine 20 mg/m² and methotrexate 50 mg/m² every week and bleomycin 15 mg/m² every two weeks. All patients were previously treated with a CDDP/5-FU regimen.Results: Forty-eight patients were evaluable for response and toxicity. After a median follow-up of 15 months, 16 patients are still alive and 32 have died. We had one complete response (2%), 12 partial responses (25%) (overall response rate 27%; 95% CI: 14%–39%), 11 stabilizations (23%) and 24 progressions (50%) of disease. Neutropenia grade 3–4 was seen in 12 patients; peripheral neurotoxicity in two patients. There were no toxic deaths.Conclusions: This regimen, administered in an outpatient setting, revealed some activity as a second-line treatment in patients with HNSC, with acceptable toxicity.     

丹参对博莱霉素所致大鼠肺纤维化保护作用的实验研究

目的:探讨丹参对博莱霉素所致大鼠肺纤维化的保护作用及其作用机理.方法:通过气管内注射博莱霉素复制大鼠肺纤维化模型,在造模后的d 1和d 7开始给予丹参注射液治疗,分别在d 7、d 28处死大鼠,对肺组织匀浆中的脂质过氧化物(MDA)、谷胱甘肽(GSH)、羟脯氨酸(HYP)和肺组织病理学变化测量.结果:在造模后d 1给予丹参注射液治疗能抑制实验性肺纤维化大鼠的肺组织匀浆中的MDA、HYP异常升高和GSH的下降,减轻其肺部的病理损害;在造模后d 7给予丹参注射液治疗,丹参治疗组与模型组上述观察指标比较无统计学差异.结论:丹参注射液可预防大鼠肺纤维化,对已形成的肺纤维化无逆转作用.     

复方鳖甲方对博莱霉素致大鼠肺纤维化的防治作用

目的探讨复方鳖甲方对气管内一次性注入博莱霉素(BLM)诱发大鼠肺纤维化的防治作用及作用机理。方法SD大鼠气管内一次性注入BLM,复制肺纤维化模型,对照组注入生理盐水。中药大、中、小剂量组于造模后第1天灌胃方式给予复方鳖甲方,各组于造模后第7,14,28天腹主动脉抽血4mL,进行动脉血气分析。左肺行组织固定,右肺支气管肺泡灌洗,膜天平法进行肺泡灌洗液表面物质(PS)活性测定。灌洗后右肺液氮速冻,进行羟脯氨酸(HYP)测定。结果7d模型组动物出现明显体重下降、低氧血症、PS系统活性异常,中药中剂量组一定程度上缓解低氧血症(P<005)及PS系统活性。大剂量及小剂量组无明显缓解趋势(P>005)。结论①博莱霉素通过损伤肺泡Ⅱ型细胞(ATⅡ),使PS系统功能异常,从而导致低氧血症的发生,复方鳖甲方中剂量组通过缓解ATⅡ细胞损伤,一定程度上改善低氧血症。②复方鳖甲方有效抑制肺泡灌洗液中的炎性渗出,从而改善肺纤维化程度。     

寡糖Lewis A模拟肽对博莱霉素诱导的小鼠急性肺炎症性损伤的抑制作用

目的考察寡糖LewisA模拟肽对肺炎症性损伤的抑制作用。方法采用博莱霉素诱导小鼠肺产生炎症损伤 ,采用病理切片法观察LewisA模拟肽对炎症的影响。结果早期注射寡糖LewisA模拟肽可以抑制博莱霉素诱导的小鼠肺炎症性损伤。结论寡糖LewisA模拟肽可能作为抑制肺炎症性损伤的药物。