山核桃树枝水煎剂对荷瘤小鼠增效减毒作用的研究

[目的]探讨山核桃树枝水煎剂(DJM)对S180荷瘤小鼠化疗后的增效减毒作用及其作用机制。[方法]通过测定外周血白细胞数量、骨髓微核率、胸腺指数和脾指数,观察DJM对化疗小鼠的增效减毒作用。[结果]DJM能够降低荷瘤小鼠的骨髓微核率,提高荷瘤小鼠外周血白细胞数量,使胸腺指数和脾指数明显改善。[结论]DJM在荷瘤机体中的抑瘤作用可能是通过调节荷瘤机体异常的免疫抑制状态,抑制肿瘤基因表达来达到的;DJM对应用化疗药物环磷酰胺(CTX)治疗的荷瘤小鼠具有增效减毒作用。     

Insights into the infective properties of YpfΦ, the Yersinia pestis filamentous phage

YpfΦ is a filamentous phage that infected Yersinia pestis, the plague bacillus, during its emergence. Using an experimental transduction approach, we show here that this phage has the capacity to infect with variable efficiencies, all three pathogenic Yersinia species as well as Escherichia coli. Like other Inovirus phages, its genetic organization comprises three functional modules necessary for the production of infectious virions. Upon infection, YpfΦ integrates into the chromosomal dif site, but extrachromosomal forms are also frequently observed. Several pieces of evidence suggest that the absence of chromosomal YpfΦ in natural non-Orientalis Y. pestis isolates results from a higher chromosomal excision rate rather than from a defective integration machinery. A resident YpfΦ confers some protection against a superinfection. In contrast to other filamentous phages, the incoming YpfΦ genome inserts itself between two copies of the resident prophage. This analysis thus unravels infective properties specific to YpfΦ.     

Macranthoside B,a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo

Macranthoside B (MB) is a hederagenin saponin extracted from the flower bud of Lonicera macranthoides. In this study, we defined the anticancer effect of MB both in vitro and in vivo using cell proliferation assays and xenograft tumor growth assays. Our data indicate that MB inhibits the proliferation of various kinds of cancer cells with IC₅₀ values in the range of 10–20 μM. Moreover, the volume and weight of xenograft tumors in nude mice treated with 5 mg/kg MB were decreased remarkably compared to those of the vehicle control group. Furthermore, DAPI staining and flow cytometry analysis with Annexin V/PI double staining revealed that more apoptotic cells were observed following MB treatment. In addition, degradation of PARP (poly-ADP-ribose polymerase), and activation of the caspase cascade for intrinsic pathways were observed. We also found that the expression of Bcl-2 protein decreased and the protein level of Bax increased which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that MB exhibited strong anti-tumor effect and mitochondrion-mediated apoptosis induction involved in it.     

参苓胶囊对实验性肿瘤的治疗及对化疗药减毒作用研究

目的：研究参苓胶囊对小鼠移植性肿瘤S180肉瘤,H22肝癌和Lewis肺癌的抗肿瘤作用及对环磷酰胺（CTX）所致小鼠免疫功能抑制的保护作用。方法：根据抗癌药物筛选标准进行体内抑瘤试验。采用CTX制备免疫功能低下模型,测定参苓胶囊与CTX配伍对小鼠白细胞数、胸腺指数、脾指数和NK细胞活性的影响。结果：不同浓度的参苓胶囊对小鼠移植性肿瘤S180肉瘤,H22肝癌和Lewis肺癌均有抑制作用,其中高剂量组效果最佳,抑制率分别为44．8％,52．2％,43．3％（P〈0．01）,且对小鼠体重生长无明显影响。参芩胶囊可明显减少CTX所致的小鼠白细胞下降,免疫器官重量和NK细胞活性降低等副作用。结论：参苓胶囊具有明显的抗肿瘤和免疫增强作用。     

小剂量环磷酰胺在类风湿关节炎的临床应用

目的：探讨小剂量环磷酰胺治疗类风湿关节炎（RA）的可行性、有效性及安全性。方法：40例患者分为小剂量环磷酰胺组与甲氨蝶呤组,评价药物疗效及不良反应。结果：小剂量环磷酰胺治疗组患者耐受良好,临床指标有所改善,关节压痛数、肿胀数、晨僵时间、ESR和CRP明显降低P〈0．05．差异有显著性。治疗前后肝肾功能、血、尿常规比较均未见明显异常改变。结论：小剂量环磷酰胺治疗类风湿关节炎是一种简单、有效、安全的治疗方案。     

Regulation of cellular therapy in Australia

Use of cellular products for therapeutic purposes has predominantly been unregulated in Australia until recently. Transplant of haemopoietic progenitor cells (HPC) for bone marrow regeneration is now a routine treatment for many disorders with an established mechanism of facility accreditation. However, other cellular therapies do not have any form of accreditation, are not well evaluated and may be associated with significant risks. On 31 May 2011 the Therapeutic Goods Administration (TGA) implemented a long heralded regulatory biologicals framework for cell and tissue based therapies. The framework currently excludes human HPC, organs for direct transplantation and reproductive materials which are already covered by various forms of existing peer review and accreditation. This new framework is a practical approach for applying regulation based on the risk of the product to the recipient with four classes of product. Class 1 is reserved for the least regulated products and currently does not contain any proposed products. Class 2 will be for minimally manipulated products which will only require manufacturing compliance and evaluation against product and other mandatory standards before entry onto the Australian Register of Therapeutic Goods (ARTG). Class 3 and 4 products will be more than minimally manipulated and these cells and tissues may be used in a non-homologous manner. Class 3 and 4 products will represent a spectrum of risk where Class 4 therapies will represent the highest potential risk to the recipient, with the same requirements for Class 2 approvals but with additional requirements for comprehensive evaluation of a dossier for quality, safety and efficacy of the product. The extent of this quality, safety and efficacy data will depend upon the nature of the product and its associated risks, but will be more comprehensive for Class 4 as opposed to Class 3 products. The only truly contentious feature of this framework is the extremely high cost for dossier evaluation and the puzzling absence of an orphan drug scheme for biologicals.     

Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate‐related osteonecrosis of the jaws: can they be utilized as risk markers?

Purpose: The purpose of this retrospective study was to examine the possibility of utilizing serum C‐terminal telopeptide cross‐link of type I collagen (s‐CTX) and serum osteocalcin (s‐OC) as risk markers for oral bisphosphonate‐related osteonecrosis of the jaws (BRONJ). Patients and methods: The s‐CTX values and the s‐OC values were measured from 23 patients (one male, 22 females) diagnosed with BRONJ using clinical and radiographic examinations. The two biochemical markers were evaluated during a regular checkup for osteoporosis management. For the control group of s‐CTX study, s‐CTX values were obtained from 61 independently recruited postmenopausal women who have been on bisphosphonate therapy for >6 months. The s‐CTX values of the ONJ group and the control group were compared. Because of retrospective nature of this study, the control group for s‐OC study could not be established. A single sample t‐test was performed for the s‐OC value from the ONJ group. Result: Twenty‐three ONJ patients had taken alendronate for osteoporosis treatment, and the s‐CTX testing results were low levels of 10–192 pg/ml (mean: 93.2±49.4 pg/ml). Mean of s‐CTX of the control (n=61) was 125±85.7 pg/ml. The duration of BP therapy ranged between 1 and 10 years (4.82±2.6). The s‐OC level was estimated between 0.2 and 5.4 ng/ml (1.91±1.51 ng/ml). The mean s‐CTX value of the control group was higher but without significance (P=0.12). The s‐OC values of the ONJ group were significantly lower than the lowest value of the reference range (P<0.001). Conclusion: As a result of the s‐CTX and s‐OC testings at the diagnosis of BRONJ, the values of the two markers were decreased. The decrease of the s‐OC values implies a problem during the bone‐formation process. Therefore, we can assume that in this patient group, invasive dental surgery contributes to an increase in the risk of BRONJ incidence. This result may imply that, during bisphosphonate therapy, simultaneous consideration of s‐CTX showing inhibition of bone resorption and s‐OC indicating the degree of bone formation might be a set of risk markers assessing risk prediction for BRONJ before invasive dental surgery. To cite this article:
Kwon Y‐D, Ohe J‐Y, Kim D‐Y, Chung D‐J, Park Y‐D. Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate‐related osteonecrosis of the jaws: can they be utilized as risk markers?
Clin. Oral Impl. Res. 22 , 2011; 100–105.
doi: 10.1111/j.1600‐0501.2010.01965.x     

The Association Between Cysteine,Bone Turnover,and Low Bone Mass

Background With the identification of hyperhomocysteinemia as a risk factor for developing osteoporosis, the contribution of thiols metabolically linked with homocysteine (tHcy) may be of importance. Cysteine (Cys) is formed from tHcy and is involved in bone metabolism via incorporation into collagen and cysteine protease enzymes. Methods We investigated the association of plasma Cys and related thiols, the bone turnover markers C-telopeptide (CTX) and procollagen type 1 N propeptide (P1NP) and folate and vitamin B₆ with calcaneal bone mineral density (BMD) in 328 postmenopausal British women grouped according to their BMD measurement. Results Subjects with low BMD had a significantly lower plasma Cys concentration (146.3 vs. 177.7 μmol/l, p < 0.0001), a significantly higher recent fracture rate (30.9% vs. 16.4%, p = 0.017), and a significantly higher percentage of current smokers (26.4% vs. 7.3%. p = 0.003) than those with normal BMD. Additionally, they had a significantly lower plasma Cys, and higher plasma tHcy and CTX, than those with osteopenia. In the whole population, Cys was significantly associated with BMD, weight, height, smoking habit, log creatinine, Cys-Gly, log tHcy, and log folate, but the significant positive association of Cys with BMD was maintained after correction for all other variables (r = 0.197, p = 0.003). After weight, Cys was the next most significant predictor of BMD in a stepwise multiple linear regression model. Conclusion Our study suggests a significant association between plasma Cys and BMD. A reduced Cys concentration, possibly modulated by smoking, or reduced flux from tHcy, may lead to reduced availability for collagen formation. Increased osteoclast activation, possibly as a result of relative hyperhomocysteinemia, may lead to increased Cys utilization in cysteine proteases.     

晚期上皮性卵巢癌术后顺铂腹腔灌注联合化疗疗效观

目的探讨顺铂（Cisplatin,DDP）腹腔灌注联合环磷酰胺（Cyclophosphamide,CTX）化疗治疗卵巢癌患者术后的疗效及预后因素。方法对2000年6月至2005年6月间入住我院的晚期卵巢癌患者术后43例进行回顾性分析,所有患者都经初次手术,化疗方案为PC（CTX iv＋DDP腹腔灌注）,分别为1-~12个疗程不等,分析他们的药物反应以及预后情况。结果Ⅲ期患者中CR10例,PR 14例,SD6例,PD1例,总有效率（overall response rate,ORR）为77.4%。Ⅳ期患者CR3例,PR5例,SD3例,PD1例,PR5例,SD3例,PD1例,ORR为66.7%,两组无显著差异。但Ⅲ期同Ⅳ期患者3年生存率及5年生存率均有显著性差异。43例无进展生存PFS（progression-free survival,PFS）为21.5个月,平均生存时间为37.5个月。结论顺铂腹腔灌注联合CTX化疗治疗卵巢癌是有效而且安全的,预后与病理类型、组织分级、术后残留癌大小及化疗疗程相关。