Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

Introduction

BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.

Methods

Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-like^CGH status, others as non-BCRA-like^CGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE₉₀C) chemotherapy.

Results

Among patients with BRCA-like^CGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE₉₀C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-like^CGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-like^CGH tumors were ER-positive.

Conclusions

Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-like^CGH patients) and those without benefit (non-BRCA-like^CGH patients).     

新疆紫草颗粒剂与汤剂对药物流产效果影响的比较性研究

目的:比较新疆紫草颗粒剂与紫草汤剂对米非司酮配伍米索前列醇药物流产效果的影响,及不良反应。方法:将648例妊娠38-45　d、要求终止妊娠的妇女,随机分成3组,各组在米非司酮配伍米索前列醇药物流产时分别加服紫草颗粒剂或安慰剂或紫草汤剂,对3组的流产效果、出血时间、月经恢复时间等及不良反应进行观察。结果:紫草颗粒剂组和汤剂组的完全流产率(97.74%、97.70%)、平均出血时间(12.0±4.1　d、12.7±3.8　d)均无显著性差异(P均>0.05),且均显著优于安慰剂组(91.90%、14.3±4.8　d)(P均<0.05)。3组药物流产后月经恢复时间均无显著性差异。但紫草汤剂服用时有明显异味。结论:　紫草颗粒剂祛除了紫草的异味,服用方便,对其提高药物流产疗效与紫草汤剂相同,有必要进一步探讨。     

Medical School Ranking and Medical Student Vocational Identity

Phenomenon: Vocational identity may play an important role in physicians' healthy professional development. Allopathic medical students' vocational identity may bear a relationship to the level of emphasis placed on research versus service at their medical school. Approach: Social mission score (SMS) and the US News and World Report (USNWR) research ranking (year 2011) were used as schools' national rankings for service and research, respectively. A questionnaire was sent to 960 3rd-year medical students from 24 allopathic medical schools between January and April 2011. The scale for vocational identity was created using the responses from the Vocational Identity Scale (9 items), and we used an established cutoff from a previous study to categorize those students who had “strong” vocational identity. Findings: After categorizing allopathic medical schools into four groups based on SMS rankings, we found that medical students who attended allopathic medical schools from the two highest SMS ranking groups were more likely to report scores reflecting strong vocational identities—odds ratio [OR] = 2.9, 95% confidence interval (CI) [1.8, 4.7] and OR = 2.5, 95% CI [1.6, 4.0], respectively. In contrast, we did not find any associations between students from allopathic medical schools with high USNWR rankings and likelihood of reporting scores reflecting strong vocational identities. Insights: Social mission scores for allopathic medical schools may potentially serve as predictors of professional and vocational identity development. Further research is needed to better understand these findings, as this is one of the first studies both to examine allopathic medical students' sense of vocational identity and to explore the use of SMS rankings as predictors of medical students' professional development.     

宫颈癌组织Raf激酶抑制蛋白和NF—κBp65表达及其临床意义

目的研究宫颈癌组织中Raf激酶抑制蛋白（RKIP）和核因子xBp65（NF-κBp65）的表达,探讨二者表达之间的相关性及其与宫颈癌各临床病理因素之间的关系。方法用免疫组织化学方法检测69例宫颈癌组织、37例宫颈上皮内瘤变组织和18例正常宫颈组织的RKIP和NF-κBp65表达,并分析其与宫颈癌临床病理学特征的关系。结果宫颈癌组织中RKIP的表达低于宫颈上皮内瘤变及正常宫颈组织,而NF-κBp65的表达高于宫颈上皮内瘤变及正常宫颈组织,差异有统计学意义（Hc=45．124、38．107,Z=4．309～5．159,P〈O．01）;RKIP和NF—κBp65在宫颈癌组织中的表达均与临床分期、有无淋巴结转移及肿瘤分化程度有关（χ^2=5．150～11．917,P〈0．05）。宫颈癌组织中RKIP与NF-κBp65的表达呈显著负相关（r=-0．464,P〈O．01）。结论RKIP表达的减少或缺失与宫颈癌的发生、发展密切相关,RKIP表达的减少或缺失可能通过上调NF—κBp65的表达促进宫颈癌的侵袭和转移。     

TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme

SummaryPurpose In order to improve the survival of patients with a glioblastoma multiforme tumor (GBM), new therapeutic strategies must be developed. The use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing Ligand) seems a promising innovative therapy. The aim of this study was to quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2 and TRAIL on primary GBM specimens and to correlate this expression with survival.Experimental design Expression of TRAIL and TRAIL-receptors was assessed by immunohistochemistry, both quantitatively (% of positive tumor cells) and semi-quantitatively (staining intensity) within both the perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR of GBM tissue was performed to show expression of TRAIL receptor mRNA.Results Immunohistochemistry showed a slight diffuse intracytoplasmic and a stronger membranous staining for TRAIL and TRAIL receptors in tumor cells. Semi-quantitative expression of TRAIL showed a significantly higher expression of TRAIL in the perinecrotic zone than in the intermediate zone of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was positively correlated with survival (P=0.02). Multivariate analysis of TRAIL-R1 within the study group (n=62) showed that age, gender, staining intensity, antigenic load, % of TRAIL-R1 expression, were not statistically correlated with survival however radiotherapy was significantly correlated (multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity: P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058; radiotherapy: P=0.0001). Subgroup analysis of patients who had received radiotherapy (n=47) showed a significant association of % of TRAIL-R1 expression and the antigenic load of TRAIL-R1 with survival (multivariate analysis: P=0.036, respectively, P=0.023).Multivariate analysis of TRAIL-R2 staining intensity and antigenic load, within the study group (P=0.004, respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004), showed a significant association with survival. RT-PCR analysis detected a negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of astrocytic tumors (P=0.03).Conclusions TRAIL-R1 and TRAIL-R2 expression on tumor cells are independent prognostic factors for survival in patients with a glioblastoma multiforme. Both receptors could be targets for TRAIL therapy. As TRAIL-R2 is more expressed, in comparison with TRAIL-R1, on GBM tumor cells, TRAIL-R2 seems to be of more importance as a target for future TRAIL therapy than TRAIL-R1.     

Seizures in children with low-grade tumors： outcome after tumor resection and risk factors for uncontrolled seizures

OBJECT： The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS： The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses.     

内镜下切开术治疗难治性食管癌术后吻合口狭窄的疗效

目的 探究食管支架置入术(ESP)和内镜下切开术(EIM)在难治性食管癌术后吻合口狭窄治疗中的应用效果.方法 将70例难治性食管癌术后吻合口狭窄患者按照手术方式不同分为ESP组(n=41)与EIM组(n=29).对比两组患者临床疗效、吞咽困难评分及并发症发生情况.结果 两组患者总有效率比较,差异无统计学意义(P>0.0...     

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.     

胃酸抑制剂不会增加老年患者术后肺炎的发病风险

本研究在于确定胃酸抑制剂是否会增加选择性手术患者术后发生肺炎的风险。 此项人群前瞻性队列研究于1992年4月1日-2008年3月31日在加拿大开展。年龄大于65岁已确定进行选择性手术的患者入组。将本年度在手术前服用过两种或以上胃酸抑制剂的患者以及术前90天内服用过至少一种胃酸抑制剂的患者入试验组,     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.