A MEK/PI3K/HDAC inhibitor combination therapy for KRAS mutant pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, metastatic disease with limited treatment options. Factors contributing to the metastatic predisposition and therapy resistance in pancreatic cancer are not well understood. Here, we used a mouse model of KRAS-driven pancreatic carcinogenesis to define distinct subtypes of PDAC metastasis: epithelial, mesenchymal and quasi-mesenchymal. We examined pro-survival signals in these cells and the therapeutic response differences between them. Our data indicate that the initiation and maintenance of the transformed state are separable, and that KRAS dependency is not a fundamental constant of KRAS-initiated tumors. Moreover, some cancer cells can shuttle between the KRAS dependent (drug-sensitive) and independent (drug-tolerant) states and thus escape extinction. We further demonstrate that inhibition of KRAS signaling alone via co-targeting the MAPK and PI3K pathways fails to induce extensive tumor cell death and, therefore, has limited efficacy against PDAC. However, the addition of histone deacetylase (HDAC) inhibitors greatly improves outcomes, reduces the self-renewal of cancer cells, and blocks cancer metastasis in vivo. Our results suggest that targeting HDACs in combination with KRAS or its effector pathways provides an effective strategy for the treatment of PDAC.     

四肢关节专用低场强MRI评估对膝关节损伤的诊断价值

目的：分析四肢关节专用低场强MRI诊断膝关节损伤的临床应用价值。 方法：于2004-12/2005-10解放军总医院全军骨科研究所收治经手术、关节镜检查或临床证实的膝关节损伤患者40例（43个膝关节）。应用Atorscan0.2T永磁型四肢关节专用低场强磁共振机,对膝关节损伤的MRI表现进行分析。 结果：四肢关节专用低场强MRI对半月板、前交叉韧带、骨挫伤等均可作出正确诊断。 结论：四肢关节专用低场强MRI对膝关节损伤的综合诊断具有重要意义,是膝关节损伤较理想的一种非创伤性检查方法。     

Amine-assisted solubilization of unsubstituted zinc phthalocyanine for film deposition purposes

Typical zinc phthalocyanines (ZnPc) exhibit poor solubility in common solvents and, hence, are processed into thin films mostly from the vapor phase. The present work discloses how these limitations can be effectively overcome. Specifically, highly concentrated molecular solutions of unsubstituted ZnPc are prepared by combining a weakly structured ZnPc polymorph with binary liquid systems composed of a π-accepting solvent and a simple nitrogenous base, such as ammonia or tertiary aliphatic amine. The amine-assisted solubilization of ZnPc is rationalized by quantitative analysis of optical spectra and electrostatic potential maps of the dye molecule. A volatile aminoalcohol is proposed in order to rationally modify the habit of ZnPc crystallites and concurrently to produce uniform deposition of the crystallites by drop-casting the dye solutions onto a glass substrate. Finally, a versatile algorithm for wet-processed ZnPc films is declared.

Wet-processing of unsubstituted zinc phthalocyanine into polycrystalline films is mastered.     

X-ray diagnosis of cardiac insufficiency in acute myocardial infarct]

Practical medicine needs a simple method for detecting the presence and severity of left ventricular insufficiency in acute myocardial infarction. Radiography of the lungs may help in solving this problem. Our idea of the X-ray picture of the lungs in pulmonary circulation congestion is now almost complete. The X-ray picture is determined by the degree of left ventricular insufficiency. The results of lung radiography of 225 patients admitted to the intensive care department for acute myocardial infarction are discussed. Alveolar pulmonary edema was diagnosed in 22.7%, interstitial pulmonary edema in 42.7%, pulmonary plethora in 27%, and mild abnormalities in 7.6% of cases. Comparison of the findings of clinical and X-ray examination in 111 patients showed that severe disorders of pulmonary circulation are detected by the X-ray method four times more frequently.     

肌腱玻璃化法冷冻保存的体外实验

目的:目前临床上常用低温冷冻法来保存同种异体肌腱,但操作较复杂费时,并且所保存的肌腱活性较低而限制其应用。采用已筛选的玻璃化法冷冻保存鸡屈趾深肌腱,并将复温后的玻璃化肌腱进行体外检测,探索其作为肌腱移植材料的可行性。方法:实验于2003-11/2005-02在解放军总医院骨科研究所完成。①实验材料及分组:来亨鸡16只,雄性,体质量2.5kg左右,随机分为2组,玻璃化组为玻璃化肌腱,新鲜肌腱组为新鲜肌腱,每组8只。②实验过程:切取来亨鸡屈趾深肌腱,置入玻璃化液内快速投入液氮保存2周制备玻璃化肌腱。③实验评估:将2组肌腱在体外进行大体、组织学及超微结构观察,羟脯氨酸含量测定,生物力学性能检测,并对两组肌腱进行细胞培养与鉴定。结果:①玻璃化组肌腱的大体、组织学及超微结构与新鲜肌腱组相似,其细胞及细胞外结构得以良好保存。②应用碱解法测定玻璃化肌腱内的羟脯氨酸含量为69.27mg/g,与新鲜肌腱组间差异无统计学意义。③玻璃化组肌腱破裂强度为165.58MPa,弹性模量1.41GPa,与新鲜肌腱组的力学性能差异无统计学意义。④将玻璃化组肌腱进行细胞培养,细胞第8天自组织块长出,第21天后传代,培养3代后出现明显的退化现象,其生物学特性与新鲜肌腱组相似。⑤将两组肌腱培养的细胞分别进行免疫组织化学染色,经鉴定均为肌腱细胞。结论:玻璃化法保存的肌腱具有良好的细胞活性、细胞外结构及力学性能,其生物学及生物力学特性无明显变异。     

The Mechanism of the Development of Macrophage Tolerance in Tumor Microenvironment

Bulletin of Experimental Biology and Medicine - Bacteria forming the resident microbiome of the tumor are an integral component of its microenvironment. The interaction of the tumor microbiome with...     

Applying a Developmental Framework to the Self‐Regulatory Difficulties of Young Children with Prenatal Alcohol Exposure: A Review

Prenatal alcohol exposure (PAE) can be associated with significant difficulties in self‐regulatory abilities. As such, interventions have been developed that focus on improving varying aspects of self‐regulation for this population. The application of a multilevel theoretical framework that describes the development of self‐regulation during early childhood could further advance the field. First, this framework could assist in elucidating mechanisms in the trajectories of early adjustment problems in this population and, second, informing the development of more precise assessment and interventions for those affected by PAE. The aims of the current review were to provide an overview of the self‐regulatory framework proposed by Calkins and colleagues (e.g., Calkins, 2007; Calkins and Fox, 2002); examine the self‐regulatory difficulties that are commonly experienced during infancy (i.e., 0 to 2 years) and early childhood (i.e., 3 to 8 years) in children with PAE in the context of the developmental framework; and describe how the framework can inform the development of future assessment and intervention provision for young children with PAE. The application of a developmental framework, such as proposed by Calkins and colleagues, allows for a systematic and theoretically driven approach to assessment and intervention programs for young children with PAE.