Drug discovery strategies for acute radiation syndrome

Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.

Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.

Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.     

Chornobyl radiation—congenital anomalies: A persisting dilemma

We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not‐Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not‐Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of NDTs and MIC are significantly higher than in not‐Polissia. In Polissia, the prevalence rates of NDTs and MIC are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re‐ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate, and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken.     

用Lyman NTCP模型分析原发性肝癌三维适形放疗引起的放射性肝病

目的建立原发性肝癌三维大分割适形放疗Lyman NTCP模型的参数和探讨放射性肝病的影响因素。方法109例患者进行大分割三维适形放疗,其中93例患者肝硬化Child-Pugh分级A级,16例为B级。患者每星期治疗3次,每次间隔48h,(4．8±0．5)Gy/次,平均剂量(53．5±5．5)Gy。用最大拟然比方法分别得到Child-A和Child-B患者Lyman模型中的NTCP参数。结果共有17例发生放射性肝病,发生在Child-A组8例,Child-B组9例。多因数分析表明,肝硬化分级程度是与放射性肝病相关的独立因素(P=0．000)。所有患者的NTCP参数为n=1．1,m=0．35,TD_(50) (1)=38．5Gy；Child-A级为n=1．1,m=0．28,TD_(50)(1)=40．5Gy；Child-B级为n=0．7,m=0．43,TD_(50)(1)=23Gy。结论肝硬化分级是预测放射性肝病发生的危险因子。Child-B患者进行适形放疗易引起放射性肝病。     

3DCRT技术治疗原发性肝癌的临床剂量学研究

目的探讨3DCRT技术治疗原发性肝癌的方法、处方剂量与疗效的关系。方法27例有随访结果的肝癌患者,对其肿瘤体积大小、位置、处方剂量及生存期作回顾性总结。结果治疗后肿瘤局部控制率为85.2%(23/27),1年生存率为70.4%(19/27),2年生存率为55.6%(15/27),3年生存率为33.3%(9/27)。所有病人无放射性肝炎等严重副反应发生。结论3DCRT技术治疗不宜手术的肝癌是一种无创而有效的治疗方法,可提高肝癌的局部控制率,不良反应轻微,病人生存质量得到提高。     

健血升白冲剂对小鼠造血功能的影响

目的：研究健血升白冲剂对小鼠血液系统的影响。方法：以骨髓细胞计数，白细胞计数和血象为指标，观察健血升白冲剂对正常小鼠和化学及放射损伤小鼠的影响。结果：健血升白冲剂明显增加正常小鼠白细胞计数（Ｐ＜００１），显著改善环磷酰胺诱导小鼠白细胞和骨髓细胞的减少作用（分别为Ｐ＜００５，Ｐ＜００１），并能显著增加６０Ｃｏ放射损伤小鼠骨髓细胞（Ｐ＜００１）和白细胞（Ｐ＜００１）。结论：健血升白冲剂对化学及放射损伤小鼠血液系统有明显的保护及改善作用。是一个有开发价值的药物。