High expression of Lewis<Superscript>y/b</Superscript>antigens is associated with decreased survival in lymph node negative breast carcinomas

Introduction  

There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewis^y and Lewis^b antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewis^y/b binding antibody that binds to native and extended Lewis^y and Lewis^b haptens, displaying no cross reactivity with H type 1, H type 2, Lewis^x or normal blood group antigens.     

Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro- intestinal endocrine tissue, anterior pituitary and other tissues. We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1. We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism. There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands). One case of sporadic MEN1 was proven to be a new MEN1 mutation. Eight different mutations were observed more than once in FMEN1. Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene. Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene. No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).      

Effect of the UK Postcode Lottery on Survival of Patients with Metastatic Renal Cancer: an Audit of Outcomes in Patients with Metastatic Renal Cancer Suitable for Treatment with Tyrosine Kinase Inhibitors

AimsTo determine whether primary care trusts’ agreement or refusal to fund sorafenib or sunitinib affects outcomes for patients with metastatic renal cell carcinoma.Materials and methodsThis retrospective audit was conducted in a tertiary referral centre for urological cancer. Requests to prescribe drugs not approved by the National Institute for Health and Clinical Excellence are recorded on a trust database. We obtained details of all requests made for sunitinib and sorafenib for patients with renal cell carcinoma since licence in 2006. Outcome measures analysed were overall survival measured from the date of request for funding and hospital resource use as measured from Payment by Results data. Known prognostic factors and the patient's Index of Multiple Deprivation score were assessed at baseline as potential confounders of survival difference.ResultsSeventy-nine patients were identified. The groups were similar with respect to prognostic factors and Index of Multiple Deprivation scores. Thirty-seven and eight patients had funding approved for sunitinib and sorafenib, respectively; 21 and 13 were turned down. Seven patients who were denied funding received one or other of these drugs by self-funding treatment. Survival was longer for patients who received treatment with a drug for which they had applied for funding than for those who did not (hazards ratio 0.46; 95% confidence interval 0.21–1.01; χ² = 3.80; 1 d.f.; P = 0.05); the advantage was similar for patients receiving sunitinib (hazards ratio = 0.49; 95% confidence interval 0.18–1.36; χ² = 1.86; 1 d.f.; P = 0.17) and sorafenib (hazard ratio = 0.44; 95% confidence interval 0.11–1.69; χ² = 1.58; 1 d.f.; P = 0.21). Overall National Health Service resource use apart from funding for the renal cancer drugs was similar for both groups.ConclusionsCompared with patients receiving treatment, patients denied access to sunitinib and sorafenib had substantially worse survival outcomes, despite receiving treatment from the same clinical team. Access to the new drugs did not have an effect on overall use of National Health Service resources by funded patients. Modern treatments for advanced renal cancer should be available to all National Health Service patients with the disease.     

Interleukin 17–producing T helper cells in alloimmunity

Interleukin (IL) 17 is a proinflammatory cytokine already known to play a defense role against microbes and a pathogenic role in a number of autoimmune diseases. Although IL-17 can be produced by a variety of cells including neutrophils, CD8⁺, NK, and gamma-delta T cells, the concept of IL-17–secreting CD4⁺ T helper cells (Th17), distinct from Th1 and Th2, recently emerged. Herein, we discuss arguments in favor of a Th17-mediated alternative pathway of allograft rejection based on clinical and experimental observations drawn from the literature. We also discuss the complex interplays among regulatory T cells and Th17 cells in the allogeneic context.     

Donor T-cell development in host thymus after heterotopic limb transplantation in mice

We developed a mouse model of heterotopic limb transplantation in which we took advantage of Thy1.1 and Thy1.2 congenic strains to track and characterize donor T cells, to determine the role of recipient's thymus in mixed T-cell chimerism induction as well as transplant immunocompetence. The vascularized Thy1.1 limb graft composed of femur, muscle, and skin (VBT) survived long-term in more than 87.5% of Thy1.2 recipients. Percentages of donor-type Thy1.1 T cells increased from day 30 to 90 in thymus and spleen of recipients. Most peripheral donor T cells displayed a na?ve phenotype and a few others were regulatory T cells. Thymectomy prevented peripheral T-cell chimerism. Congenic VBT in immunodeficient RAG mice restored their ability to reject skin allografts. These observations suggest that donor T cells differentiated in host thymus might contribute to maintenance of mixed chimerism after transplantation of tissue composite grafts that include vascularized bone.     

Coronary artery anomalies diagnosed by magnetic resonance angiography

Coronary artery anomalies are uncommon entities that may be associated with sudden death. Because of its 2‐D projection imaging nature, conventional X‐ray coronary angiography may not accurately delineate the origins and course of aberrant coronary arteries with respect to the great vessels. Non‐invasive, cross‐sectional imaging techniques such as coronary CT angiography and magnetic resonance angiography are increasingly used in clinical practice to diagnose coronary artery anomalies. Although this study reviews coronary artery anatomy and selected anomalies as seen with true fast imaging with steady‐state precession magnetic resonance angiography, the information provided is equally applicable to electrocardiogram‐gated coronary CT angiography.     

人脐血CD34+ 细胞静脉移植对急性心肌梗死大鼠血流动力学指标和超声心动图指标的影响

目的:观察人脐带血CD34 细胞移植治疗急性心肌梗死大鼠的可行性及其对心功能的影响。方法:实验于2006-03/10在首都医科大学附属北京友谊医院完成。①选取11～13周龄雄性SD大鼠40只,随机数字表法分为假手术组10只、模型对照组15只、细胞移植组15只。脐血由北京市脐血干细胞库提供,采自无妊娠并发症、身体健康、新生儿足月分娩(37～40周)孕妇,均签署知情同意书,自愿捐献用于科学研究和临床治疗。②一次性血袋抽取孕妇脐带血80～120mL,按5∶1比例加入60g/L羟乙基淀粉,4℃420r/min离心8min;去除红细胞,留取上层含有核细胞的血浆层,4℃1180r/min离心10min,去除血浆,留取有核细胞,测CD34 含量为0.35%～0.42%。③模型对照组、细胞移植组大鼠建立急性心肌梗死模型,麻醉后切开第4、5肋间肌,暴露心脏,在动脉圆锥和左心耳间、距左心耳下1mm处(相当于左前降支近段)用Prolene线结扎。假手术组只挂线不结扎。根据左室前壁颜色变白、活动减弱和心电图ST段明显抬高作为急性心肌梗死模型成功标志。④术后3h内,细胞移植组经尾静脉注射0.5mL人脐血干细胞悬液(含干细胞2×1010L-1),模型对照组经尾静脉注射0.5mL生理盐水。饲养30d。⑤分别于术前、术后1d和术后30d进行超声心动图检测。并于术后30d进行血流动力学检测。结果:假手术组挂线过程中死亡1只,模型对照组造模及细胞移植过程死亡4只,细胞移植组造模及细胞移植过程死亡5只。①人脐血CD34 细胞移植30d后对大鼠血流动力学的影响:与假手术组比较,模型对照组左室收缩压、左室压力最大变化率均明显减小(t=2.16～5.14,P均<0.05),左室舒张末压、心率均明显增加(t=2.01～8.86,P<0.01或0.05);与模型对照组比较,细胞移植组左室收缩压、左室压力最大变化率均明显增加(t=2.72～2.35,P均<0.05),左室舒张末压明显减小(t=4.24,P<0.01),心率无明显变化(t=1.67,P>0.05)。②人脐血CD34 细胞移植前后超声心动图检查结果:与假手术组比较,术前模型对照组和细胞移植组各指标无明显变化;术后1,30d模型对照组和细胞移植组左室舒张末期内径、左室收缩末期内径、左室舒张末容积、左室收缩末容积均明显增加(t=2.14～9.98,P<0.05或0.01),左室前壁厚度、左室后壁厚度、左室射血分数、左室短轴缩短率均明显减小(t=2.52～14.23,P<0.05或0.01)。与模型对照组比较,术前和术后1d细胞移植组各指标无明显变化,但术后30d左室舒张末期内径、左室收缩末期内径、左室舒张末容积、左室收缩末容积均明显减小(t=2.07～7.04,P<0.05或0.01),左室前壁厚度、左室后壁厚度、左室射血分数、左室短轴缩短率均明显增加(t=3.22～9.85,P均<0.01)。结论:在未使用免疫抑制剂的情况下,人脐带血CD34 细胞静脉移植可明显改善急性心肌梗死大鼠各项心功能指标,未见明显不良反应。