鲨鱼软骨血管生成抑制因子的纯化和功能

以中国东海鲸鲨软骨为原料,通过盐抽提、丙酮分级沉淀、离子交换层折、分子筛层析、高效液相色谱等步骤,获得鲨鱼软骨血管生成抑制因子－Ｉ（ｓｈａｒｋ ｃａｒｔｉｌｇａｅ ａｎｇｉｏｇｅｎｅｓｉｓ ｉｎｈｉｂｉｔｏｒｙ ｆａｃｔｏｒ－Ｉ,ＳＣＡＩＦ－Ｉ）,对其分子量、抑制血管生成及抑制肿瘤生长活性进行了研究。结果显示ＳＣＡＩＦ－Ｉ分子量１８ｋＤ,在细胞和整体水平上显著抑制新血管生成,显著抑制小鼠肿瘤的生长     

PYK2 is overexpressed in chronic lymphocytic leukaemia: A potential new therapeutic target

Chronic Lymphocytic Leukaemia (CLL) is the most common adult B-cell leukaemia and despite improvement in patients' outcome, following the use of targeted therapies, it remains incurable. CLL supportive microenvironment plays a key role in both CLL progression and drug resistance through signals that can be sensed by the main components of the focal adhesion complex, such as FAK and PYK2 kinases. Dysregulations of both kinases have been observed in several metastatic cancers, but their role in haematological malignancies is still poorly defined. We characterized FAK and PYK2 expression and observed that PYK2 expression is higher in leukaemic B cells and its overexpression significantly correlates with their malignant transformation. When targeting both FAK and PYK2 with the specific inhibitor defactinib, we observed a dose–response effect on CLL cells viability and survival. In vivo treatment of a CLL mouse model showed a decrease of the leukaemic clone in all the lymphoid organs along with a significant reduction of macrophages and of the spleen weight and size. Our results first define a possible prognostic value for PYK2 in CLL, and show that both FAK and PYK2 might become putative targets for both CLL and its microenvironment (e.g. macrophages), thus paving the way to an innovative therapeutic strategy.     

A beam model for focused proton pencil beams

IntroductionWe present a beam model for Monte Carlo simulations of the IBA pencil beam scanning dedicated nozzle installed at the Skandion Clinic. Within the nozzle, apart from entrance and exit windows and the two ion chambers, the beam traverses vacuum, allowing for a beam that is convergent downstream of the nozzle exit.Materials and methodsWe model the angular, spatial and energy distributions of the beam phase space at the nozzle exit with single Gaussians, controlled by seven energy dependent parameters. The parameters were determined from measured profiles and depth dose distributions. Verification of the beam model was done by comparing measured and GATE acquired relative dose distributions, using plan specific log files from the machine to specify beam spot positions and energy.ResultsGATE-based simulations with the acquired beam model could accurately reproduce the measured data. The gamma index analysis comparing simulated and measured dose distributions resulted in >95% global gamma index pass rates (3%/2 mm) for all depths.ConclusionThe developed beam model was found to be sufficiently accurate for use with GATE e.g. for applications in quality assurance (QA) or patient motion studies with the IBA pencil beam scanning dedicated nozzles.     

Simulation of dose distribution and secondary particle production in proton therapy of brain tumor

AimThe aim of this study is simulation of the proton depth-dose distribution and dose evaluation of secondary particles in proton therapy of brain tumor using the GEANT4 and FLUKA Monte Carlo codes.BackgroundProton therapy is a treatment method for variety of tumors such as brain tumor. The most important feature of high energy proton beams is the energy deposition as a Bragg curve and the possibility of creating the spread out Bragg peak (SOBP) for full coverage of the tumor.Materials and methodsA spherical tumor with the radius of 1 cm in the brain is considered. A SNYDER head phantom has been irradiated with 30−130 MeV proton beam energy. A PMMA modulator wheel is used for covering the tumor. The simulations are performed using the GEANT4 and FLUKA codes.ResultsUsing a modulator wheel, the Spread Out Bragg Peak longitudinally and laterally covers the tumor. Flux and absorbed dose of secondary particles produced by nuclear interactions of protons with elements in the head are considerably small compared to protons.ConclusionsUsing 76.85 MeV proton beam and a modulator wheel, the tumor can be treated accurately in the 3-D, so that the distribution of proton dose in the surrounding tissues is very low. The results show that more than 99% of the total dose of secondary particles and protons is absorbed in the tumor.     

富勒烯的生物活性研究进展

90年代初以来,富勒烯类化合物的生物活性逐渐引起人们的注意,初步研究表明在抗艾滋病毒、酶活性抑制、切割DNA、光动力学治疗等方面具有独特的功效.此类化合物在生化、医学、药物学等领域有良好的应用前景.     

Ca^2＋与细胞凋亡

Ｃａ＾２＋在某些因素诱导的细胞凋亡中起着重要信使作用。细胞内Ｃａ＾２＋浓度上升可来源于胞外Ｃａ＾２＋内汉、内库钙动员或者二者兼之。     

Curcumin stably interacts with DNA hairpin through minor groove binding and demonstrates enhanced cytotoxicity in combination with FdU nucleotides

We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV–Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two ? H of curcumin heptadiene chain are closely positioned to the A₁₆-H8 and A₁₇-H8, while G₁₂-H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy.     

Cord blood–derived cytokine-induced killer cells combined with blinatumomab as a therapeutic strategy for CD19+ tumors

Background

Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19⁺ malignancies.