Targeting UPR branches,a potential strategy for enhancing efficacy of cancer chemotherapy

Cancer cells are often exposed to cell intrinsic stresses and environmental perturbations that may lead to accumulation of unfolded and/or misfolded proteins in...     

中药益智的化学成分研究

采用正反相硅胶、Sephadex LH-20凝胶、MCI树脂等层析技术从中药益智95%乙醇提取物的乙酸乙酯部位分离得到13个化合物,运用现代波谱技术分别鉴定为:益智酮甲(1,yakuchinone A)、益智醇(2,oxyphyllacin-ol)、白杨素(3,chrysin)、rhamnocitrin(4)、oxyphyllenodiol A(5)、oxyphyllenodiol B(6)、nootkatone(7)、dehydro-noot-katone(8)、7-epi-teucrenone(9)、oxyphyllenone A(10)、oxyphyllenone B(11)、原儿茶酸(12,protocatechuic acid)和琥珀酸(13,succinic acid)。其中化合物4、13为首次从该植物中分得,化合物8为新的天然产物。     

The Roles of Hypoxia-Inducible Factors in Regulating Neural Stem Cells Migration to Glioma Stem Cells and Determinating Their Fates

The mortality of patients with malignant gliomas remains high despite the advancement in multi-modal therapy including surgery, radio- and chemotherapy. Glioma stem cells (GSCs), sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Accordingly, targeting GSCs proves to be a promising avenue of therapeutic intervention. The specific tropism of NSCs to GSCs provides a novel platform for targeted delivery of therapeutic agents. Tropism and mobilization of NSCs are enhanced by hypoxia through upregulating chemotactic cytokines and activating several signaling pathways. Moreover, hypoxia-inducible factors (HIFs) produced under hypoxic microenvironment of the stem cell niche play critical roles in the growth and stemness phenotypes regulation of both NSCs and GSCs. However, the definite cellular and molecular mechanisms of HIFs involvement in the process remain obscure. In this review, we focus on the pivotal roles of HIFs in migration of NSCs to GSCs and potential roles of HIFs in dictating the fates of migrated NSCs and targeted GSCs.     

Elastic priors to dynamically borrow information from historical data in clinical trials

Use of historical data and real-world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is to effectively borrow information from historical data while maintaining a reasonable type I error and minimal bias. We propose the elastic prior approach to address this challenge. Unlike existing approaches, this approach proactively controls the behavior of information borrowing and type I errors by incorporating a well-known concept of clinically significant difference through an elastic function, defined as a monotonic function of a congruence measure between historical data and trial data. The elastic function is constructed to satisfy a set of prespecified criteria such that the resulting prior will strongly borrow information when historical and trial data are congruent, but refrain from information borrowing when historical and trial data are incongruent. The elastic prior approach has a desirable property of being information borrowing consistent, that is, asymptotically controls type I error at the nominal value, no matter that historical data are congruent or not to the trial data. Our simulation study that evaluates the finite sample characteristic confirms that, compared to existing methods, the elastic prior has better type I error control and yields competitive or higher power. The proposed approach is applicable to binary, continuous, and survival endpoints.     

Combined effects of avasimibe immunotherapy,doxorubicin chemotherapy,and metal–organic frameworks nanoparticles on breast cancer

CD8⁺ T cells play a vital role in cancer immunotherapy and can be shaped by metabolism. Avasimibe is an acyl coenzyme A-cholesterol acyltransferase (ACAT) inhibitor, which has been clinically verified safe in other phase Ⅲ clinical trials. It can potentiate the killing function of CD8⁺ T cells by modulating cholesterol metabolism. Doxorubicin (DOX) is an anticancer drug widely used in many cancers to induce tumor cell apoptosis. Unfortunately, DOX also can induce toxic and side effects in many organs, compromising its usage and efficacy. Herein, we report the combinational usage of avasimibe and a safe pH sensitive nano-drug delivery system composing of DOX and metal–organic frameworks nanoparticles (MNPs). Our findings demonstrated that DOX–MNPs treatment inhibited tumor growth with good safety profile and avasimibe treatment combined DOX–MNPs treatment exhibited a better efficacy than monotherapies in 4T1 breast cancer therapy.     

CO2浓度增加和施氮对栓皮栎幼苗生理生态特征的影响

通过人为控制CO₂浓度(700、400 μmol·mol^-1)和氮素水平(120 kg N·hm^-2),研究了CO₂浓度增加和氮沉降及其交互作用对北界(辽宁庄河)栓皮栎幼苗生理生态特征的影响.结果表明: CO₂浓度升高使栓皮栎幼苗叶片的形态、光合色素含量和氮含量有减小的趋势,暗呼吸速率较对照降低63.3%,可溶性糖增加2.6%.氮沉降对栓皮栎叶片的形态和光合色素含量有明显的促进作用,叶N含量增加而K含量降低,N/K值增加26.7%.CO₂和N交互作用对幼苗叶形态和光合作用有明显的促进作用,叶片最大净光合速率和光饱和点分别是对照的1.4倍和2.6倍,暗呼吸速率和光补偿点分别降低65.9%和50.0%.CO₂浓度升高和N沉降均对栓皮栎幼苗生长有一定的促进作用,可能导致栓皮栎分布界线北移.     

SCNVSim: somatic copy number variation and structure variation simulator

Background

Somatically acquired structure variations (SVs) and copy number variations (CNVs) can induce genetic changes that are directly related to tumor genesis. Somatic SV/CNV detection using next-generation sequencing (NGS) data still faces major challenges introduced by tumor sample characteristics, such as ploidy, heterogeneity, and purity. A simulated cancer genome with known SVs and CNVs can serve as a benchmark for evaluating the performance of existing somatic SV/CNV detection tools and developing new methods.

Results

SCNVSim is a tool for simulating somatic CNVs and structure variations SVs. Other than multiple types of SV and CNV events, the tool is capable of simulating important features related to tumor samples including aneuploidy, heterogeneity and purity.

Conclusions

SCNVSim generates the genomes of a cancer cell population with detailed information of copy number status, loss of heterozygosity (LOH), and event break points, which is essential for developing and evaluating somatic CNV and SV detection methods in cancer genomics studies.