MR imaging of focal liver lesions: comparison between turbo spin-echo and conventional spin-echo pulse sequences

The aim of this study was to compare conventional spin-echo (CSE)T ₂-weighted (T2W) images with turbo spin-echo (TSE) T2W pulse sequences in their ability to detect focal liver lesions. Seventy-eight consecutive patients with focal liver lesions were entered into this study. All patients were imaged using the gradient-echo (GE) sequence with the breath-hold technique forT ₁-weighted (T1W) images, and CSE and TSE sequences for T2W images. Qualitative evaluation included lesion detection (number of lesions detected) and conspicuity (extent of visualization of lesional borders); quantitative evaluation included the signal-to-noise (S/N) ratio and the contrast-to-noise (C/N) ratio. TSE showed the best performance in terms of lesion detection; however, the difference between TSE and CSE was significant only in the case of benign cysts (p<0.01). Conspicuity was higher with TSE and CSE, and lower with GE. The S/N and C/N ratios of the two T2W sequences were also comparable, and better than those of GE. However, the combined use of GE and TSE resulted in improved lesion detection. The results show that, because the acquisition time is greatly reduced with TSE sequences, these should be considered as first-line approach to magnetic resonance imaging of the liver for the study of focal lesions.     

Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.     

Retrospective analysis for evaluation of the value of contrast-enhanced MRI in patients treated with breast conservative therapy

Purpose The aim of this study was to assess the value of contrast-enhanced (c.-e.) MRI in the follow-up of patients with conservatively treated breast cancer since detection and exclusion of malignancy may interfere significantly with posttherapeutic changes within the treated breast. Material and methods A total of 207 patients with a history of limited surgery and radiation therapy underwent MR imaging, 40 patients were examined 0–12 months and 167 patients were examined later than 12 months after radiotherapy. Suspicious or indeterminate findings were suggested by clinical examination or conventional imaging in 80 studies. In 127 women, MRI was performed within breast tissue that was difficult to assess due to scarring or dense breast tissue. Results Recurrent carcinoma was confirmed in 27 patients by surgical biopsy. All 27 carcinomas, except for one with a slow signal increase, demonstrated early rise of signal intensity on dynamic T1-weighted contrast enhanced images. During the first year after therapy, the diagnostic accuracy could not be improved by additional use of c.-e. MRI. Differentiation between posttherapeutic changes and recurrent carcinoma was frequently not possible because of strong and sometimes early and ill-circumscribed enhancement. Later than 12 months after therapy enhancement decreased significantly, thus the false positive calls could be reduced from 49 (conventional imaging) to 12 (conventional imaging plus MRI). A total of 12 of 26 recurrences and multifocality in 4/5 cases were diagnosed by MR imaging alone at this time interval. Conclusion In the first year after therapy, c.-e. MRI is only indicated in selected cases. The results later than 12 months emphasize that c.-e. MRI may contribute significant additional information. It allows better distinction of posttherapeutic fibrosis from recurrent carcinoma and proved to be able to detect recurrent disease more sensitive and at an earlier stage.     

Automatic measurement of volume percentage stroma in endometrial images using texture segmentation

The popularity of digital microscopy and tissue microarrays allow the use of high-throughput imaging for pathology research. To coordinate with this new technique, it is essential to automate the process of extracting information from such high amount of images. In this paper, we present a new model called the Subspace Mumford-Shah model for texture segmentation of microscopic endometrial images. The model incorporates subspace clustering techniques into a Mumford-Shah model to solve texture segmentation problems. The method first uses a supervised procedure to determine several optimal subspaces. These subspaces are then embedded into a Mumford-Shah objective function so that each segment of the optimal partition is homogeneous in its own subspace. The method outperforms a widely used method in bioimaging community called k-means segmentation since it can separate textures which are less separated in the full feature space, which confirm the usefulness of subspace clustering in texture segmentation. Experimental results also show that the proposed method is well performed on diagnosing premalignant endometrial disease and is very practical for segmenting image set sharing similar properties.     

子宫下段受累可能为Ⅰ期内膜癌辅助放疗的不良预后因素

目的　探讨子宫下段受累对Ⅰ期子宫内膜癌术后放疗患者的预后作用。方法　回顾性分析1999年1月至2012年12月在北京协和医院进行术后放疗的Ⅰ期子宫内膜癌患者265例，中位年龄53岁，病理类型主要为子宫内膜样腺癌(226例，85.3％)。根据病理结果是否有子宫下段受累分为两组：子宫下段受累组和子宫下段未受累组，比较两组患者的预后因素和临床治疗结果，并对其中的高危和高中危患者进行亚组分析。主要研究终点包括总生存率、无进展生存率、局部区域复发率、远处转移率和治疗失败率。使用Kaplan-Meier法统计生存率，不同组间生存率的比较使用Log-rank检验，使用Cox比例风险回归模型进行预后因素分析。结果　所有Ⅰ期内膜癌患者的5年总生存率和无进展生存率分别为92.8%和89.7%，5年局部区域复发率、远处转移率和治疗失败率分别为4.5%、6.4%和7.8%。单因素分析显示，子宫下段受累是影响总生存率和无进展生存率的相关因素（P= 0.015,0.035）。Cox比例风险回归模型显示，子宫下段受累组患者的总生存率和无进展生存率更低（P=0.041, RR=0.346, 95% CI: 0.125~0.959; P=0.041, RR=0.411, 95% CI: 0.175~ 0.963）。亚组单因素分析显示，在高危和高中危患者中，子宫下段受累是影响治疗失败率的相关因素（P=0.034）。结论　子宫下段受累可能是影响Ⅰ期内膜癌辅助放疗患者总生存率和无进展生存率的不良预后因素；在高危和高中危患者中，子宫下段受累主要与治疗失败的发生相关。     

Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells

Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.     

肿瘤PET药物的现状和展望

随着正电子发射计算机断层显像技术(PET)的研发,PET药物在肿瘤科学研究及临床应用中具有越来越重要的作用。本文在肿瘤代谢显像、肿瘤细胞凋亡显像、反义显像、受体显像及基因表达监测等方面集中介绍肿瘤PET药物的进展情况及其发展前景。     

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.