Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15–16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted ‘U’ dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm³; and C3-0.2%: 462.9 ± 75.9 mm³). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm³; C3-0.02%: 1401.5 ± 555.6 mm³), as was tumor number (C3-2%: 10.7 ± 1.3 mm³; C3-0.02%: 8.1 ± 1.1 mm³). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.     

Cardiovascular magnetization transfer ratio imaging compared with histology: A postmortem study

Cardiovascular magnetization transfer ratio (MTR) imaging by steady state free precession is a promising imaging method to assess microstructural changes within the myocardium. Hence, MTR imaging was correlated to histological analysis. Three postmortem cases were selected based on a suspicion of myocardial infarction. MTR and T₂‐weighted (T_2w) imaging was performed, followed by autopsy and histological analysis. All tissue abnormalities, identified by autopsy or histology, were retrospectively selected on visually matched MTR and T_2w images, and corresponding MTR values compared with normal appearing tissue. Regions of elevated MTR (up to approximately 20%, as compared to normal tissue), appearing hypo‐intense in T_2w‐images, revealed the presence of fibrous tissue in microscopic histological analysis. Macroscopic observation (autopsy) described scar tissue only in one case. Regions of reduced MTR (up to approximately 20%) corresponded either to (i) the presence of edema, appearing hyperintense in T_2w‐images and confirmed by autopsy, or to (ii) inflammatory granulocyte infiltration at a microscopic level, appearing as hypo‐intense T_2w‐signal, but not observed by autopsy. Findings from cardiovascular MTR imaging corresponded to histology results. In contrast to T_2w‐imaging, MTR imaging discriminated between normal myocardium, scar tissue and regions of acute myocardial infarction in all three cases. J. Magn. Reson. Imaging 2014;40:915–919 . © 2013 Wiley Periodicals, Inc.     

Onyx HD-500 Liquid Embolic Agent for the Embolization of Broad-Based Saccular Intracranial Aneurysms: A Case Study

Over the years, many different techniques have been used to treat brain aneurysms. Traditionally, open surgery or craniotomy was required for aneurysm clipping, but since the mid 1980s the endovascular treatment of aneurysms has become increasingly popular. The mainstay of endovascular aneurysm treatment has been embolization with platinum coils (a.k.a. “coiling”). However, despite advances in endovascular techniques, such as balloon remodeling and intracranial stent placement, it remains difficult to achieve the complete and permanent occlusion of many broad-based saccular aneurysms. Onyx HD-500 (eV3 Neurovascular, Irvine, CA), a liquid embolic agent, is the latest Food and Drug Association-approved device to be used in attempt to overcome the challenge of occluding broad-based intracranial aneurysms.In this case study, we describe the clinical and procedural issues involved in the treatment of a patient with a large, symptomatic intracranial aneurysm using Onyx HD-500.     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（下）

本刊经Philip M．Meyers博士代表写作组授权,将“ Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis”译为中文在本刊刊登。标准中对患者的选择、颅内动脉狭窄程度的判断、最佳内科治疗、围手术期处理、血管内治疗、术后并发症等,进行了规范化总结,拟为今后的临床试验和研究的规范化确定标准,以保证结果的可比性,对神经介入医师具有重要的指导意义。     

Further genotype – phenotype correlations in neurofibromatosis 2

Selvanathan SK, Shenton A, Ferner R, Wallace AJ, Huson SM, Ramsden RT, Evans DG. Further genotype–phenotype correlations in neurofibromatosis 2. Neurofibromatosis 2 (NF2) is caused by mutations in the NF2 gene predisposing carriers to develop nervous system tumours. Different NF2 mutations result in either loss/reduced protein function or gain of protein function (abnormally behaving mutant allele i.e. truncated protein potentially causing dominant negative effect). We present a comparison between the clinical presentations of patients with mutations that are predicted to produce truncated protein (nonsense/frameshift mutations) to those that results in loss of protein expression (large deletions) to elucidate further genotype–phenotype correlations in NF2. Patients with nonsense/frameshift mutations have a younger age of diagnosis and a higher prevalence/proportion of meningiomas (p = 0.002, p = 0.014), spinal tumours (p = 0.004, p = 0.004) and non‐VIII cranial nerve tumours (p = 0.006, p = 0.003). We also found younger age of diagnosis of vestibular schwannomas (p = 0.007), higher mean numbers of cutaneous lesions (p = 0.003) and spinal tumours (p = 0.006) in these patients. With respect to NF2 symptoms, we found younger age of onset of hearing loss (p = 0.010), tinnitus (p = 0.002), paraesthesiae (p = 0.073), wasting and weakness (p = 0.001) and headaches (p = 0.049) in patients with nonsense/frameshift mutations. Our comparison shows, additional, new correlations between mutations in the NF2 gene and the NF2 disease phenotype, and this further confirms that nonsense/frameshift mutations are associated with more severe NF2 symptoms. Therefore patients with this class of NF2 mutation should be followed up closely.     

Metabotropic glutamate receptor 2 and 3 gene expression in the human prefrontal cortex and mesencephalon in schizophrenia

Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in schizophrenia. We characterized mGluR2 and 3 mRNA in the human prefrontal cortex (PFC) and mesencephalon, and then compared cases with schizophrenia to matched controls. In the human brain, both receptors were expressed in the PFC and, unlike the rodent, in dopaminergic (DA) cell groups. In schizophrenia, we found significantly higher levels of mGluR2 mRNA in the PFC white matter. The expression of mGluR2, 3 in DA cells provide a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference may be critical to understanding rodent models in schizophrenia.