Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast

Introduction

Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting.

Methods

We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies.

Results

Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03).

Conclusions

The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline.     

EB病毒LMP2A和EB病毒BZLF1融合基因反转录病毒表达载体的构建

目的:将LMP2A和BZLF1基因进行融合同时可发挥LMP2A诱导特异性CTL和BZLF1基因诱导潜伏期EBV进入裂解期复制的作用,协同杀伤EBV阳性肿瘤细胞。实验拟构建含EB病毒潜伏膜蛋白2A编码基因和即刻早期基因融合基因的反转录病毒表达载体,并筛选建立携带该基因的高滴度产毒细胞系。方法:实验于2006-08/2007-08在济宁医学院微生物教研室和青岛大学医学院微生物教研室进行。应用反转录-聚合酶链反应分别获得潜伏膜蛋白2A和即刻早期基因编码序列的cDNA,采用剪接式重叠延伸技术将两段基因通过多肽接头(Gly_4Ser)_3的DNA序列进行连接,构建融合基因Z2A。将融合基因Z2A定向插入逆转录病毒表达载体pMSCVpuro,形成重组质粒pMSCVpuro-Z2A,脂质体法将pMSCVpuro-Z2A转染反转录病毒包装细胞PT67。嘌呤霉素筛选产毒细胞克隆,扩大培养产毒细胞克隆,收获病毒进行滴度测定,RT-PCR检测产毒PT67细胞目的基因的转录表达。结果:限制性酶切、PCR及测序鉴定证实Z2A正确插入逆转录病毒表达载体,筛选获得了稳定产毒的嘌呤霉素抗性细胞克隆,收获病毒的滴度为7.8×10~6 CFU/L,且重组逆转录病毒在PT67细胞能有效转录。结论:携带Z2A基因的重组反转录病毒表达载体pMSCVpuro-Z2A构建成功,转染PT67细胞后包装出重组反转录病毒,进而筛选获得了能转录表达Z2A的产毒细胞系PT67-Z2A。     

AN UNUSUAL CASE OF LEFT PARADUODENAL HERNIA

Paraduodenal hernias are the commonest form of intra-abdominal hernia. We report on a rare paraduodenal hernia involving the duodenojejunal recess.     

The impact of disability on performance in a high-stakes postgraduate surgical examination: a retrospective cohort study

ObjectiveDespite rising numbers of doctors in the workforce with disabilities, little is known about the impact of disabilities on postgraduate performance. To ensure all groups are treated fairly in surgical training, it is essential to know whether any attainment differences exist in markers of surgical performance. To address this gap, we assessed the impact of disabilities on performance on the Intercollegiate Membership of the Royal College of Surgeons examination (MRCS).DesignRetrospective cohort study.SettingSecondary care.ParticipantsAll UK MRCS candidates attempting Part A (n = 9600) and Part B (n = 4560) between 2007 and 2017 with linked disability data in the UK Medical Education Database (https://www.ukmed.ac.uk) were included.Main outcome measuresChi-square tests and correlation coefficients established univariate associations with MRCS performance, while multiple logistic regressions identified independent predictors of success.ResultsThough MRCS Part B pass rates were similar (p = 0.339), candidates with registered disabilities had significantly lower first-attempt Part A pass rates (46.3% vs. 59.8%, p < 0.001). Candidates with disabilities also performed less well in examinations taken throughout school and medical school, and after adjusting for prior academic performance and sociodemographic predictors of success, logistic regression found that candidates with disabilities were no less likely to pass MRCS than their peers (odds ratio 1.04, 95% confidence interval 0.66 to 1.62). No significant variation was found in MRCS performance between type of disability or degree of limitations caused by disability (p > 0.05).ConclusionAlthough candidates with registered disabilities performed less well in formal, written examinations, our data indicate that they are as likely to pass MRCS at first attempt as their peers who achieved similar grades at high school and medical school. In order to enable equity in career progression, further work is needed to investigate the causes of attainment differences in early career assessments.     

Human cochlear expressed sequence tags provide insight into cochlear gene expression and identify candidate genes for deafness

To identify candidate genes for human hearing disorders and to understand better human hearing at the molecular level, we constructed a human cochlear cDNA library. An aliquot of the unsubtracted cochlear library was contributed to the IMAGE Consortium at Lawrence Livermore National Laboratory for the generation of expressed sequence tags (ESTs) by the Merck/WashU EST project. Over 4000 ESTs were developed from the cochlear cDNA library and deposited in the GenBank EST database. Sequence clustering shows that the majority of clones are in low copy numbers, demonstrating the high complexity of the library. The sequences of 1388 cochlear ESTs (33%) match 517 known human genes. Among these are genes previously shown to cause both syndromic and non- syndromic hearing loss. A number of the cochlear ESTs show high homology to non-human genes, suggesting new gene family members or human homologs of animal genes. We also report the chromosomal map positions of 437 cochlear ESTs. These provide positional candidate genes for 18 different non-syndromic hearing disorders. A Human Cochlear EST Database web site (http://www.bwh.partners. org/pathology ) has been created to provide access to the cochlear clone data for gene discovery investigations.