Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death

Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death, suggesting that DRAM2 is involved in cell death. Thus, we propose that reduced expression of DRAM2 may contribute to enhanced cell survival in tumor cells.     

Molecular constitution of breast but not other reproductive tissues is rich in growth promoting molecules: A possible link to highest incidence of tumor growths

In the current study we tested if highest incidence of benign as well as cancer growths in breast tissue is due to constitutive molecular composition of this tissue. To delineate the molecular basis, we compared the expression of nine functional gene modules (total 578 genes) that regulate major positive growth and negative inhibitory signals in normal breast with two other reproductive tissues, ovary and uterus. We present data to demonstrate that breast tissues constitutively have very highly elevated levels of several growth promoting molecules and diminished levels of inhibitory molecules which may, in part, contribute for highest incidence of tumor growths in this tissue.     

Acute activation of acid ceramidase affects cytokine-induced cytotoxicity in rat islet β-cells

Ceramidase hydrolyzes ceramide and produces sphingosine as a substrate of sphingosine kinase (SPHK), which transforms sphingosine to sphingosine-1-phosphate. It has been reported that cytokines elicit SPHK activation in rat β-cells. As a sphingosine provider, ceramidase should also be activated. In our previous work, we showed that the increase in mRNA and protein levels in cytokine-treated INS-1 rat β-cells resulted in chronic activation of neutral ceramidase. Here we found that acid ceramidase (AC) is activated by cytokines at an early stage via tyrosine phosphorylation. In addition, basal AC activity was first detected in INS-1 cells and isolated rat islets, and cytokine-induced cell growth was significantly repressed when AC was pharmacologically inhibited.     

Pancreatic cancer cells activate CCL5 expression in mesenchymal stromal cells through the insulin-like growth factor-I pathway

Mesenchymal stromal cells (MSCs) have a critical role in cancer progression and metastasis. Despite extensive studies of the physiological responses in cancer cells, the molecular mechanisms regulating gene expression in MSCs by cancer cells remain undefined. Here we demonstrate that CC chemokine ligand 5 (CCL5) expression was increased in MSCs co-cultured with pancreatic cancer cells (PCCs), and this activation was dependent on extracellular insulin-like growth factor (IGF-I). Moreover, CCL5 induction in MSCs was required for the activation of IGF-I pathway in PCCs. These results reveal a link between the IGF-I pathway in PCCs and CCL5 pathway in MSCs through the interaction of those cells.     

心脏术后急性肾损伤的研究进展

急性肾损伤（Acute Kidney Injury,AKI）是心脏术后较常见且较严重的并发症,明显增加患者的住院费用,并且增加手术死亡率。研究发现术前肾功能不全、糖尿病、及外周血管疾病等是术后AKI的危险因素。最新的研究发现一些新的生物学标准物可以为我们早期诊断心脏术后AKI的发生的提供帮助。而一旦出现AKI,选择适当药物治疗和肾脏替代治疗,可以保护肾功能,改善AKI患者的预后。     

乳腺错构瘤X线及病理特征分析

目的：探讨乳腺错构瘤的病理及影像学特征。方法：对11例乳腺错构瘤患者的临床特征、X线征象及病理表现进行回顾性分析。结果：患者平均年龄为46岁（26-58岁）,10例可触及肿块（9例患者自己发现,1例体检摄片时发现）,还有1例未能触及肿块。左乳7例,右乳4例,5／11（45．5％）肿块位于外上象限。11例钼靶X线平片均发现乳腺肿块,多数肿块呈卵圆形,边界清楚。肿块平均最大直径为6．Ocm（2．5-13．0cm）,6／11（54．5％）肿块呈混合密度影。4／11例（36．4％）术前X线确诊。镜下：肿瘤由数量不等、杂乱无章的乳腺导管、小叶和成熟的脂肪细胞及纤维纽织混杂组成。结论：混合密度影是其特异性X线表现,不同个体肿瘤各成分比例的不同导致X线表现差异较大。     

Current progress in epigenetic research for hepatocarcinomagenesis

Hepatocellular carcinoma is the main type of primary liver cancer, and also one of the most malignant tumors. At present, the pathogenesis mechanisms of liver cancer are not entirely clear. It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis, caused by the genetic and epigenetic aberrance. In the past, people generally thought that genetic mutation is a key event of tumor pathogenesis, and somatic mutation of tumor suppressor genes is in particular closely associated with oncogenesis. With deeper understanding of tumors in recent years, increasing evidence has shown that epigenetic silencing of those genes, as a result of aberrant hypermethylation of CpG islands in promoters and histone modification, is essential to carcinogenesis and metastasis. The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms, other than changes in the underlying DNA sequence. Specific epigenetic processes include DNA methylation, genome imprinting, chromotin remodeling, histone modification and microRNA regulations. This paper reviews recent epigenetics research progress in the hepatocellular carcinoma study, and tries to depict the relationships between hepatocellular carcinomagenesis and DNA methylation as well as microRNA regulation. Supported by National Basic Research Program of China (Grant No. 2006CD910402) and Science and Technology Commission of Shanghai Municipality (Grant No. 05DZ22201 and 08JC1416400).     

Nanotechnology‐based molecular photoacoustic and photothermal flow cytometry platform for in‐vivo detection and killing of circulating cancer stem cells

In‐vivo multicolor photoacoustic (PA) flow cytometry for ultrasensitive molecular detection of the CD44+ circulating tumor cells (CTCs) is demonstrated on a mouse model of human breast cancer. Targeting of CTCs with stem‐like phenotype, which are naturally shed from parent tumors, was performed with functionalized gold and magnetic nanoparticles. Results in vivo were verified in vitro with a multifunctional microscope, which integrates PA, photothermal (PT), fluorescent and transmission modules. Magnet‐induced clustering of magnetic nanoparticles in individual cells significantly amplified PT and PA signals. The novel noninvasive platform, which integrates multispectral PA detection and PT therapy with a potential for multiplex targeting of many cancer biomarkers using multicolor nanoparticles, may prospectively solve grand challenges in cancer research for diagnosis and purging of undetectable yet tumor‐initiating cells in circulation before they form metastasis. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Prosthetic valve endocarditis: management strategies and prognosis

Background Prosthetic valve endocarditis (PVE) is a rare and serious complication after heart valve replacement; its optimal management strategy, though, still needs to be defined. Objective To study the clinical, microbiological and echocardiographic characteristics of PVE and to analyse the influence of the adopted therapeutic strategy (medical or surgical) on short- and midterm outcome in a tertiary care centre in a developing country (Tunisia). Methods All cases of PVE treated in our institution between 1997 and 2006 were retrospectively analysed according to the modified DUKE criteria. Results A total of 48 PVE episodes were diagnosed (30 men and 18 women), mean age was 37.93 years. Twenty-eight patients (58.33%) were exclusively medically treated, whereas 20 (41.66%) were treated by a combined surgical and medical strategy. Indications for surgery were haemodynamic deterioration in eight patients (40%), annular abscess in six (30%) and persisting sepsis in six (30%). In comparison with those from the medical group, operated patients had a longer delay to diagnosis (p=0.025), were more frequently in heart failure (p=0.04) and experienced more early complications (p=0.011); they also more frequently had prosthetic dehiscence (p=0.015), annular abscesses (p=0.039) and vegetations >10 mm (p=0.008). Conversely, no differences were found between the groups in terms of age, sex, or nature of involved organisms. In-hospital mortality for the medical group was 14.28% and for the surgical group 35% (p=0.09). Conclusion PVE is a very serious condition carrying high mortality rates regardless of the adopted strategy. Our study demonstrates that, in selected patients, medical treatment could be a successful and acceptable approach. (Neth Heart J 2009;17: 56-60.)