Biosynthetic energy cost for amino acids decreases in cancer evolution.

Rapidly proliferating cancer cells have much higher demand for proteinogenic amino acids than normal cells. The use of amino acids in human proteomes is largely affected by their bioavailability, which is constrained by the biosynthetic energy cost in living organisms. Conceptually distinct from gene-based analyses, we introduce the energy cost per amino acid (ECPA) to quantitatively characterize the use of 20 amino acids during protein synthesis in human cells.

Overexpression of Gremlin 1 by sonic hedgehog signaling promotes pancreatic cancer progression.

Sonic hedgehog (SHH) signaling is an important promotor of desmoplasia, a critical feature in pancreatic cancer stromal reactions involving the activation of pancreatic stellate cells (PSCs). Gremlin 1 is widely overexpressed in cancer-associated stromal cells, including activated PSCs. In embryonic development, SHH is a potent regulator of Gremlin 1 through an interaction network.

Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high-throughput sequencing.

Circular RNAs (circRNA) are special noncoding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs (miRNA).

RNA editing derived epitopes function as cancer antigens to elicit immune responses.

In addition to genomic mutations, RNA editing is another major mechanism creating sequence variations in proteins by introducing nucleotide changes in mRNA sequences. Deregulated RNA editing contributes to different types of human diseases, including cancers. Here we report that peptides generated as a consequence of RNA editing are indeed naturally presented by human leukocyte antigen (HLA) molecules.

miR-183 inhibits autophagy and apoptosis in gastric cancer cells by targeting ultraviolet radiation resistance-associated gene.

Ultraviolet radiation resistance‑associated gene (UVRAG) regulates autophagy by promoting the formation and maturation of autophagosomes. The aim of the present study was to investigate the effects of UVRAG and UVRAG‑targeting miRNA on the regulation of autophagy and apoptosis in gastric cancer (GC). TargetScan was used to predict that miR‑183 targets the 3'‑untranslated region (UTR) of UVRAG, while the interaction between miR‑183 and the 3'‑UTR of UVRAG was assessed using a dual luciferase reporter assay.

LncRNA-FENDRR mediates VEGFA to promote the apoptosis of brain microvascular endothelial cells via regulating miR-126 in mice with hypertensive intracerebral hemorrhage.

Background: LncRNA-FENDRR is a kind of endothelial genes critical for vascular development. Moreover, miR-126 and vascular endothelial growth factor A (VEGFA) are also involved in the physiological process of vascular endothelial cells. This study aimed to the underlying mechanism of FENDRR involving miR-126 and VEGFA in hypertensive intracerebral hemorrhage (HICH).

Thrombin-Responsive, Brain-Targeting Nanoparticles for Improved Stroke Therapy.

Current treatments for ischemic stroke are insufficient. The lack of effective pharmacological approaches can be mainly attributed to the difficulty in overcoming the blood-brain barrier. Here, we report a simple strategy to synthesize protease-responsive, brain-targeting nanoparticles for the improved treatment of stroke.

Nanosizing Noncrystalline and Porous Silica Material-Naturally Occurring Opal Shale for Systemic Tumor Targeting Drug Delivery.

Opal shale, as a naturally occurring and noncrystalline silica material with porous structure, has the potential to be a drug delivery carrier. In this study, we obtained opal shale nanoparticles (OS NPs) through the techniques of ultrasonic emulsion and differential centrifugation. The OS NPs exhibited markedly lower cytotoxicity than crystalline mesoporous silica nanoparticles.

Targeting glypican-4 overcomes 5-FU resistance and attenuates stem cell-like properties via suppression of Wnt/β-catenin pathway in pancreatic cancer cells.

The existences of cancer stem cells in patients with pancreatic cancer are considered as pivotal factors contributing to chemoresistance and disease relapse. Glypican-4 (GPC4) is one of the members of the glypicans family, which underlies human congenital malformations and multiple diseases. However, its potential biological function in pancreatic cancer still remains elusive.

Plasma tyrosine and its interaction with low high-density lipoprotein cholesterol and the risk of type 2 diabetes mellitus in Chinese.

Aims/introduction: Metabolomic markers have the potential to improve the predicting accuracy of existing risk scores for type 2 diabetes mellitus. The present study aimed to test the associations between plasma tyrosine and type 2 diabetes mellitus with special attention to identifying possible cut-off points for type 2 diabetes mellitus, and its interactive effects with low high-density lipoprotein cholesterol (HDL-C) and/or high triglyceride for type 2 diabetes mellitus.

Methods: From 27 May 2015 to 3 August 2016, we retrieved the medical notes of 1,898 inpatients with type 2 diabetes mellitus as the cases, and 1,522 individuals without diabetes as the controls who attended annual medical checkups from the same tertiary care center in Jinzhou, China.

Synthesis and structure-activity relationship of N-(piperidin-4-yl)benzamide derivatives as activators of hypoxia-inducible factor 1 pathways.

Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC values of 0.12 and 0.

SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity.

Dysregulation of YAP localization and activity is associated with pathological conditions such as cancer. Although activation of the Hippo phosphorylation cascade is known to cause cytoplasmic retention and inactivation of YAP, emerging evidence suggests that YAP can be regulated in a Hippo-independent manner. Here, we report that YAP is subject to non-proteolytic, K63-linked polyubiquitination by the SCF E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1.

Elevated preoperative plasma D-dimer dose not adversely affect survival of gastric cancer after gastrectomy with curative intent: A propensity score analysis.

Objective: Elevated plasma D-dimer has been reported to be associated with advanced tumor stage and poor survival in several types of malignancies. The purpose of this study was to assess the potential impact of preoperative plasma D-dimer level (PDL) on overall survival (OS) of gastric cancer (GC) patients undergoing curative surgery by applying propensity score analysis.

Methods: A total of 1,025 curatively resected GC patients in Tianjin Medical University Cancer Institute & Hospital were enrolled.

Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung.

Objective: To evaluate the short-term efficacy and safety of apatinib alone or combined with chemotherapy in the treatment of advanced squamous cell lung cancer.

Methods: Forty patients with advanced squamous cell lung carcinoma were enrolled in this study, who were treated in Xuzhou Central Hospital from 2014 to 2015. All patients underwent first-line or more chemotherapy.

Long noncoding RNA AFAP1-AS1 predicts a poor prognosis and regulates non-small cell lung cancer cell proliferation by epigenetically repressing p21 expression.

Background: Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the role and molecular mechanism and global genes that were mediated by lncRNA AFAP1-AS1 in non-small cell lung cancer (NSCLC) remain largely unknown.

Methods: Expression of AFAP1-AS1 was analyzed in 92 NSCLC tissues and cell lines by Quantitative real time polymerase chain reaction (qRT-PCR).

Fast-Evolving Human-Specific Neural Enhancers Are Associated with Aging-Related Diseases.

The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging-related diseases and enhancers acquired after the human-chimpanzee divergence.

[Advertent problems about gastric stump cancer surgery].

Due to different disease background of gastric stump cancer(GSC) patients (benign or malignant lesion, reconstruction of digestive tract, etc.), the GSC surgical procedure and the difficulty of lymphadenectomy are also different. The extent of radical lymphadenectomy for gastric stump cancer should extend beyond D2 lymphadenectomy, according to the different backgrounds of initial disease, reconstructions, and tumor location.

A novel nomogram individually predicting disease-specific survival after D2 gastrectomy for advanced gastric cancer.

Background: Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients.

Methods: A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China.

Dasatinib promotes TRAIL-mediated apoptosis by upregulating CHOP-dependent death receptor 5 in gastric cancer.

Dasatinib, a tyrosine kinase inhibitor, has been approved for first-line treatment of leukemia and has also been evaluated for use in numerous other cancers. However, its role in gastric cancer (GC) remains unclear. Therefore, the aim of this study was to investigate how dasatinib suppresses the growth of GC cells and interacts with chemotherapeutic drugs.

A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis.

Tumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for novel therapeutic strategies. Despite multiple studies demonstrating that the mesenchymal-to-epithelial transition (MET) is critical for metastatic colonization, key regulators that initiate this transition remain unknown.

ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade.

ARID1A (the AT-rich interaction domain 1A, also known as BAF250a) is one of the most commonly mutated genes in cancer. The majority of ARID1A mutations are inactivating mutations and lead to loss of ARID1A expression , which makes ARID1A a poor therapeutic target. Therefore, it is of clinical importance to identify molecular consequences of ARID1A deficiency that create therapeutic vulnerabilities in ARID1A-mutant tumors.

Credentialing Individual Samples for Proteogenomic Analysis.

An integrated analysis of DNA, RNA and protein, so called proteogenomic studies, has the potential to greatly increase our understanding of both normal physiology and disease development. However, such studies are challenged by a lack of a systematic approach to credential individual samples resulting in the introduction of noise into the system that limits the ability to identify important biological signals. Indeed, a recent proteogenomic CPTAC study identified 26% of samples as unsatisfactory, resulting in a marked increase in cost and loss of information content.