Oral vehicle administration before radiation causes radioprotection of murine SCCVII tumors

The effect of administering various vehicles on the response to radiation of SCCVII tumors in C3H mice was investigated. When saline, 0.5% carboxymethyl cellulose solution, or 1% hydroxypropylmethyl cellulose (HPMC) solution was given orally 30 min before single 15 Gy irradiation, the tumor regrowth was significantly faster than that seen after 15 Gy treatment alone. There was no difference in this radioprotective response due to the type of vehicle. On the other hand, the tumor regrowth was similar to that seen after 15 Gy alone when saline was given intravenously 20 min before irradiation or intraperitoneally 30 min beforehand, or when 1% HPMC was given orally 2 h beforehand. Oral vehicle administration shortly before irradiation can cause radioprotection of murine tumors, probably by increasing the hypoxic fraction.     

Local administration of interleukin-11 ameliorates intestinal radiation injury in rats

Intestinal radiation injury is dose limiting during abdominal and pelvic radiotherapy and critical for the outcome after accidental whole-body radiation exposure. The multifunctional cytokine, interleukin-11 (IL-11), ameliorates the intestinal radiation response, but its clinical use is hampered by severe toxicity after systemic administration. This study addressed whether protection against intestinal radiation injury can be achieved by intraluminal administration of IL-11. Male rats underwent surgical transposition of a 4-cm small bowel loop to the scrotum. For repeated intraluminal drug administration, an ileostomy, proximal to the bowel loop in the scrotum, was created. The transposed intestinal loop was exposed to 5 Gy fractions on 9 consecutive days. Recombinant human IL-11 (rhIL-11; 2 mg/kg/d) or vehicle was given through the ileostomy from 2 days before until 2 weeks after irradiation. At 2 weeks, structural, cellular, and molecular aspects of intestinal radiation injury were assessed. rhIL-11 ameliorated structural manifestations of radiation enteropathy, including radiation injury score (6.5 +/- 0.6 in the vehicle group versus 4.0 +/- 0.3 in the IL-11 group; P = 0.001), mucosal surface area loss (0.2 +/- 0.1 versus 0.5 +/- 0.03; P < 0.0001), and intestinal wall thickening (842 +/- 66 microm versus 643 +/- 54 microm; P = 0.02), reduced postradiation transforming growth factor-beta overexpression, and reduced numbers of ED2-positive cells. Postirradiation mucosal mast cell numbers were partially restored by rhIL-11. These data show that local administration of rhIL-11 ameliorates early intestinal radiation injury and support further development of rhIL-11 to reduce manifestations of intestinal radiation injury in the clinic.     

痰热清注射液对放射性肺炎的预防作用

目的:观察痰热清注射液对急性放射性肺炎的预防作用.方法: 90例不能手术的非小细胞肺癌病人随机分入治疗组44人与对照组46人.采用适形放射治疗技术,总剂量56-64 Gy,V20 限制在20%-30%;治疗组从放疗开始到放疗结束应用痰热清注射液每天20ml静脉点滴,每连用5天,停用2天.对照组单纯放疗.结果: 治疗组和对照组放射性肺炎发生例数(率)分别是5(11.3%)和14(30.4%),两组之间有显著差别(P<0.05),且治疗组无2级及以上放射性肺炎的发生.放射性肺炎发病时间分别是放疗开始后62.2天和54.3天,差异显著(P<0.05).结论: 接受放射治疗的非小细胞肺癌患者放疗期间应用痰热清注射液能有效预防放射性肺炎的发生.     

痰热清注射液对放射性肺炎的预防作用

目的：观察痰热清注射液对急性放射性肺炎的预防作用。方法：90例不能手术的非小细胞肺癌病人随机分入治疗组44人与对照组46人。采用适形放射治疗技术,总剂量56—64Gy,V20限制在20％-30％;治疗组从放疗开始到放疗结束应用痰热清注射液每天20ml静脉点滴,每连用5天,停用2天。对照组单纯放疗。结果：治疗组和对照组放射性肺炎发生例数（率）分别是5（11．3％）和14（30．4％）,两组之间有显著差别（P〈0．05）,且治疗组无2级及以上放射性肺炎的发生。放射性肺炎发病时间分别是放疗开始后62．2天和54．3天,差异显著（P〈0．05）。结论：接受放射治疗的非小细胞肺癌患者放疗期间应用痰热清注射液能有效预防放射性肺炎的发生。     

痰热清在非小细胞肺癌后程放疗中的应用

目的 研究痰热清在非小细胞肺癌后程放疗中的应用价值。方法 放疗：肺癌后程放疗,先常规分割照射40GY后缩野加量,总量64GY。用药：于后程缩野时给予药物治疗。结果 用药组与对照组急性放射性肺炎发生率分别为33.3％和15．2％（x^2=4．433,P=0．035）,其组间差别有显著统计学意义。两组治疗后1月其急性放射性肺炎发生率下降为15．2％（x^2=4．201,P=0．04）,其差别亦有显著统计学意义。在减轻放射性肺纤维化等晚反应方面两组相似。结论 在肺癌后程治疗中,应用痰热清能减轻放疗急性反应并缩短反应持续时间,对放射性肺纤维化等晚反应无价值。     

Oral administration of cholic acid promotes growth of liver tumors initiated by diethylnitrosamine in rats.

The effect of dietary administration of cholic acid on tumorigenesis in the liver was investigated in male Fischer-344 rats after carcinogenic initiation by diethylnitrosamine (DEN); progression of liver tumors was examined in the rats fed 0.4% cholic acid-containing diet (CA group) and the rats fed standard diet (C group) at 15, 20 and 25 weeks after administration of DEN. The total bile acids and cholic acid in serum of CA group were 150 nmol/ml and 117 nmol/ml, being 31-fold and 51-fold higher than those in C group (p<0.0001, each). Serum AST and ALT were significantly higher in CA group than in C group at 15 weeks (p<0.01). Serum ALP was significantly higher in CA group than C group at each time point (p<0.01, each). Liver tumors, whose histology was hepatocellular carcinoma, developed at 15 weeks in both CA and C groups. However, tumor volume and tumor weight were significantly increased in CA group, compared to those in C group at each time point (p<0.001, p<0. 001, p<0.01, p<0.001, p<0.01 and p<0.05). The percentage of apoptotic cells in CA group at each time point was significantly lower than C group (p<0.05, p<0.01 and p<0.05). The percentage of bcl-2 positive tumor cells in C group at 20 weeks was 1.88+/-2.59%. However, it dramatically increased to 34.00+/-13.67% in CA group (p<0.0001). It was also higher in CA group than in C group at 15 and 25 weeks (p<0.05 and p<0.01). In addition, the bax-positive cells were higher in CA group than in C group at 20 weeks (p<0.05). These data suggest that oral administration of cholic acid promotes liver tumorigenesis initiated by DEN through reducing apoptosis mediated by overexpression of bcl-2.     

Gastric mucosal blood flow and gastric secretion following intravenous administration of 5-fluorouracil in anesthetized rats

 Acute gastric mucosal lesions are often observed after the intravenous administration of high doses of anticancer drugs. To investigate the acute toxic effects of such anticancer therapy on the gastric mucosa, 5-fluorouracil (5-FU) was administered intravenously to anesthetized rats. Gastric mucosal blood flow (GMBF) was measured continuously using laser Doppler velocimetry. Acid secretion was measured using a perfusion method for 1h after the administration of 5-FU. No significant change was observed with a low dose of 5-FU (50 mg/kg), but a high doses of 5-FU (100 or 200 mg/kg) caused a significant decrease in GMBF in a dose-dependent manner. The selective antagonist of the muscarinic acetylcholine receptor, pirenzepine, prevented the decrease in GMBF with high doses of 5-FU. Acid secretion decreased after the administration of 5-FU, but not significantly. This study indicates that a decrease in GMBF may be an important factor in gastric mucosal injury induced by chemotherapy. Pirenzepine may prevent the gastric mucosal lesions which are induced by the administration of 5-FU. Received: 7 December 1995/Accepted: 29 June 1996     

放射性肺炎的诊断和治疗

放射性肺炎(RP)为放射性肺损伤的一部分,其损伤与修复是由众多细胞和细胞因子等参与和相互作用的复杂的病理生理过程,给予早期诊断和治疗可减轻肺损伤,保护肺功能。临床症状和体征与感染性肺炎没有明显特异性差别,但症状轻,白细胞总数升高不明显或仅中性分类稍高。糖皮质激素有刺激白细胞升高的作用,宜使用前行检查。CT扫描诊断RP敏...     

Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats

Increased cytokine expression contributes to the pathogenesis of cancer anorexia?cachexia syndrome. Carnitine may reduce inflammation in chronic diseases. We tested the effects of L-propionylcarnitine (PC group) or saline (C group) on food intake (FI), body composition, and inflammatory status of MCA-sarcoma-bearing rats. On tumor appearance, rats were randomly assigned to daily i.p. injection of L-propionylcarnitine (250 mg/kgBW/d; n = 8) or saline (equal volume; n = 8). FI and fat-free mass wasting improved in PC rats only (p < .01 vs. controls). Cytokines? levels decreased in PC rats vs. controls (p < .02). Results suggest that carnitine may ameliorate cancer anorexia?cachexia, via reduction of the inflammatory status.     

Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer

PURPOSE: The purpose of this study was to investigate the efficacy of 2-methoxyestradiol as an antitumor and radiosensitizing agent for the treatment of human malignancy. METHODS AND MATERIALS: Two cancer cell lines with wild-type p53 status were exposed first to irradiation and then to an oral formulation of the nontoxic metabolite 2-methoxyestradiol (2ME) to stabilize p53 levels. RESULTS: Cell growth was inhibited via G1 growth and apoptosis. Subsequent in vitro growth and Tunel assays indicated that this combination was superior to radiation alone at inducing p53 protein accumulation, stabilizing p53 protein levels, and substantially reducing long-term tumor cell growth (approximately 80%) and colony formation (approximately 95%) in vitro, and inducing apoptosis. However, harboring mutated p53, H322 cell line, was relatively insensitive to such a treatment regimen. Western blot analysis revealed that growth inhibition was associated with increased levels of p53 and p21 protein accumulation. Experiments with subcutaneous tumor in a nu/nu mouse showed the combination treatment to be superior to radiation alone at reducing tumor growth ( approximately 50% reduction as compared to radiation alone) in vivo. CONCLUSION: Thus, our studies confirmed a unique strategy whereby oral administration of a nontoxic estrogen metabolite, 2ME, significantly enhanced the radiation effect on a subcutaneous tumor without any toxicity and suggesting that this strategy may be clinically useful as an adjuvant therapy.