Predicting a local recurrence after breast-conserving therapy by gene expression profiling

Introduction

To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.

Methods

By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.

Results

Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.

Conclusion

Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.     

马钱子碱抗肝细胞癌作用的实验研究

目的 探讨马钱子碱抗肝细胞癌的作用及其机制.方法 体外培养人肝癌SMMC-7721细胞,加入不同浓度的马钱子碱(2.5～400μg/ml),细胞培养72 h,MTT法测定细胞生长抑制率.Western blotting和荧光定量RT-PCR技术分别测定培养24、48、72 h肝癌细胞PCNA、Cyclin D1、FAS基因mRNA和蛋白表达.结果 随着马钱子碱用量逐渐增加,对人肝癌细胞SMMC-7721生长抑制作用增强,马钱子碱用量为320 μg/ml时对肝癌细胞生长抑制率接近100%.马钱子碱作用肝癌细胞24 h与作用48 h相比,Fas蛋白和mRNA表达差异无统计学意义(分别F=2.547,1.582,均P＞0.05),作用72 h时差异有统计学意义(分别F=1.036,1.137,均P＜0.05);PCNA和Cyclin D1的mRNA和蛋白表达各时间点差异无统计学意义(PCNA分别F=3.612,2.174,3.029;Cyclin D1分别F=2.361,2.915,1.976,均P＞0.05).结论 马钱子碱抑制肝癌细胞生长,可能通过肝癌细胞FAS基因和蛋白表达增加,诱导肝癌细胞凋亡发挥抑制作用,而与PCNA和Cyclin D1作用无关.

Abstract：

Objective To study the effect of brucine on the growth of a hepatocellular carcinoma cell line in vitro. Methods Brucine was added into a liver cancer cell line of SMMC-7721 in vitro, at drug concentration of brucine from 2. 5 μg/ml to 400 μg/ml. The inhibition rate of cell growth was measured by MTT technique after the cells were cultured for 72 hours. The protein and mRNA expression of PCNA,cyclin D1 and FAS were respectively assayed with Western blotting and fluorescent quantitation RT-PCR techniques at 24, 48, 72 h. Results The inhibition rate of liver cancer cell was near 100% when the brucine concentration was at 320 μg/ml. The protein and mRNA expression of FAS were of no significant difference at 24 h vs 48 h ( seperately F = 2. 547,1. 582, all P ＞ 0. 05 ), and significant difference existed at 24 h vs 72 h( seperately F = 1. 036, 1. 137, all P ＜ 0. 05 ). The protein and mRNA expression of PCNA,Cyclin D1 were of no significant difference between various time period( seperately PCNA F = 3.612,2. 174,3.029;Cyclin D1 F=2.361,2.915,1.976,all P＞0.05). Conclusions Brucine inhibits the growth of liver cancer cells, by inducing increased apoptosis of the cells probably through FAS overexpression.     

Influence of effective components of Qingnao Xuanqiao Fang on expression of BBB P-glycoprotein in rats with ischemia stroke

目的 比较正常及缺血损伤时大鼠血脑屏障上转运蛋白中P-糖蛋白(P-gp)时征表达及清脑宣窍方有效组分对其表达的影响.方法 线栓法制备缺血性脑中风大鼠模型,按照不同再灌注时间,模型组再分为0、0.5、1、2、6、12、24 h,采用免疫组织化学法观察正常组与模型组大鼠脑皮质及海马缺血区P-gp的表达.除假手术组外,缺血动物于术后1d,随机分为模型组、清脑宣窍方有效组分高、中、低剂量组、维拉帕米组,并于造模后1～5 d灌胃给予相应药物.末次给药后,处死动物,取材,检测大鼠脑皮质及海马区P-gp的表达.结果 免疫组织化学染色结果显示,正常组与模型组大鼠脑皮质及海马缺血区均可见P-gp阳性染色.免疫组化半定量分析表明,与正常组比较,不同再灌注时间模型组P-gp表达量均有显著性差异(P＜0.05),皮质及海马缺血区P-gp表达量均降低;与模型组比较,清脑宣窍方有效组分各剂量组及维拉帕米组对缺血性脑中风大鼠脑皮质及海马区P-gp表达量明显降低(P＜0.05).结论 在缺血性脑中风病理状态下,大鼠脑血脑屏障上转运蛋白P-gp存在一定的时征表达,而且从一定程度上反映了特定病理状态下由于蛋白表达的改变而引起的血脑屏障通透性的变化.清脑宣窍方有效组分对缺血性脑中风大鼠脑皮质及海马缺血区P-gp表达具有显著的抑制作用.     

Microbiological assessment of indoor air of a teaching hospital in Nigeria

Objective

To investigate the quality of indoor air of different wards and units of Olabisi Onabanjo University Teaching Hospital, Sagamu, to ascertain their contribution to infection rate in the hospital.

Methods

The microbial quality of indoor air of nine wards/units of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria was conducted. Sedimentation technique using open Petri-dishes containing different culture media was employed and samplings were done twice daily, one in the morning shortly after cleaning and before influx of people/patients into the wards/units and the other in the evening when a lot of activities would have taken place in these wards. Isolates were identified according to standard methods.

Results

Results showed that there was a statistically significant difference (χ² = 6.016 7) in the bacteria population of the different sampling time whereas it was not so for fungi population (χ² = 0.285 7). Male medical ward (MMW) and male surgical general (MSG) recorded the highest bacterial and fungal growth while the operating theatre (OT) was almost free of microbial burden. The bacteria isolates were Staphylococcus aureus, Klebsiella sp., Bacillus cereus, Bacillus subtilis, Streptococcus pyogenes and Serratia marscences while the fungi isolates included Aspergillus flavus, Penicillium sp., Fusarium sp., Candida albicans and Alternaria sp. Staphylococcus aureus was the predominantly isolated bacterium while Penicillium sp. was the most isolated fungus.

Conclusions

Though most of the microbial isolates were potential and or opportunistic pathogens, there was no correlation between the isolates in this study and the surveillance report of nosocomial infection during the period of study, hence the contribution of the indoor air cannot be established. From the reduction noticed in the morning samples, stringent measures such as proper disinfection and regular cleaning, restriction of patient relatives'' movement in and out of the wards/units need to be enforced so as to improve the quality of indoor air of our hospital wards/units.     

The role of the urology clinical nurse specialist in the multidisciplinary team meeting

Multidisciplinary teams (MDTs) are increasingly the preferred method of cancer care in many specialties, including urology. MDTs provide a means of improving communication between health care professionals and patients and provide co‐ordinated and timely care. As MDTs have developed, so too has the role of the specialist cancer nurse, though the concept of the clinical nurse specialist (CNS), or their involvement in the MDT are not globally universal. There is increasing evidence that the presence of the CNS in the MDT improves patient satisfaction and team effectiveness. The MDT meeting is the focal point for decision‐making about patients' care, but the roles of health care professionals in the MDT meeting are variable and poorly defined. In this paper, we examine the evidence for the role of the CNS in the urology MDT meeting, which includes communicating with colleagues and patients, co‐ordinating care, as well as facilitating research and clinical governance. We discuss the challenges faced by CNSs and how their role in MDT meetings can be strengthened to enhance their effectiveness in the MDT in general.     

直视下尿道内切开术治疗尿道狭窄20年经验总结

目的 总结直视下尿道内切开术(direct vision internal urethrotomy,DVIU)治疗尿道狭窄的经验.方法 回顾性分析1990年6月至2010年6月20年间DVIU治疗尿道狭窄或闭锁患者361的临床资料.年龄16～72岁,平均38岁.病程3～78个月,平均16个月.狭窄或闭锁长度0.2～2.0 cm,平均1.1 cm.狭窄长度≤1.0 cm 238例,其中≤0.5 cm 63例(组1),0.6～1.0 cm 175例(组2),瘢痕厚度≤1.0 cm 148例,＞1.0 cm 90例;狭窄长度1.1～2.0 cm 123例,其中1.1～1.5cm 85例(组3),1.6～2.0 cm 38例(组4),瘢痕厚度≤1.0 cm 44例,＞1.0 cm 79例.结果 361例中手术失败3例.320例获随访,随访时间12～120个月,平均42个月.因狭窄复发而接受开放手术174例(54.4%),4组中转开放手术率分别为3.3%、49.7%、83.3%和97.1%.狭窄长度≤1.0cm者获随访207例,其中瘢痕厚度≤1.0 cm转开放手术27.2%(37/136),瘢痕厚度＞1.0 cm转开放手术60.6%(43/71).狭窄长度＞1.0 cm者获随访113例,其中瘢痕厚度≤1.0 cm转开放手术78.6%(33/42),瘢痕厚度＞1.0 cm转开放手术84.5%(60/71).结论 当尿道狭窄长度≤0.5 cm时,DVIU术后转开放手术的比例明显减少;狭窄长度≤1.0 cm,瘢痕厚度≤1.0 cm者,DVIU也可获较好疗效.

Abstract：

Objective To summarize the experience and evaluate the efficacy of treatment of urethral stricture using direct visual internal urethrotomy (DVIU).Methods The clinical data of 361 patients (age range 16 -72 years, mean age 38 years) with urethral stricture who underwent urethrotomy from 1990 to 2010 was retrospectively analyzed.The disease course ranged from three months to 78 months with a mean of 16 months.The stricture length ranged from 0.2 to 2.0 cm (mean 1.1 cm).Stricture length was split into four main groups:stricture length≤0.5 cm in 63 (group 1 ), stricture length ranging between 0.6 and 1.0 cm in 175 ( group 2), stricture length ranging between 1.0 and 1.5 cm in 85 ( group 3 ) , and stricture length ranging between 1.6 and 2.0 cm in 38 ( Group 4).Of the 238 patients with length less than 1.0 cm there were 148 who's scar thickness were less than 1.0 cm, and 90 who's scar thickness were greater than 1.0 cm.Of the 123 patients with length less than 2.0 cm there were 69 who's scar thickness was less than 1.0 cm, and 54 who's scar thickness was greater than 1.0 cm.Results Three patients with DVIU failed because of long occlusion and false passage.Three hundred and twenty patients were followed-up from 12 to 120 months (mean:42).Re-openiag procedures were performed on 174 patients (54.4%) due to recurrence.The re-openiag procedure rate was 3.3%, 49.7%, 83.3% and 97.1% in Group1, Group2,Group3 and Group4, respectively.On the basis of scar thickness, of the 207 patients with stricture length less than 1.0 cm, 38 of 136 patients (27.9%) with scar thickness less than 1.0 cm underwent opening operation, and 43 of 71 patients (60.6%) with scar thickness more than 1.0 cm underwent opening operation.One hundred and thirteen patients with stricture length more than 1.0 cm, 33 of 42 patients (78.6%) with scar thickness less than 1.0 cm underwent opening operation, and 60 of 71 patients (84.5%) with scar thickness more than 1.0 cm underwent opening operation.Conclusions Good efficacy can be achieved in patients whose urethral stricture length is less than 0.5cm or whose stricture length and scar thickness is less than 1.0 cm using DVIU.