Prognostic significance of lymphocyte monocyte ratio in patients with ovarian cancer.

Background: This study aimed to systematically assess the prognostic value of lymphocyte monocyte ratio (LMR) in patients with ovarian cancer through performing a meta-analysis.

Methods: Web of Science, PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases were searched for potentially eligible studies. The baseline characteristics and relevant data were extracted.

Transcription Factor RREB1: from Target Genes towards Biological Functions.

The Ras-responsive element binding protein 1(RREB1) is a member of zinc finger transcription factors, which is widely involved in biological processes including cell proliferation, transcriptional regulation and DNA damage repair. New findings reveal RREB1 functions as both transcriptional repressors and transcriptional activators for transcriptional regulation of target genes. The activation of RREB1 is regulated by MAPK pathway.

Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy.

Oral tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor (EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs.

Synthetic Biology Speeds Up Drug Target Discovery.

As a rising emerging field, synthetic biology intends to realize precise regulations of cellular network by constructing artificial synthetic circuits, and it brings great opportunities to treat diseases and discover novel drug targets. Depending on the combination mode of different logic gates, various synthetic circuits are created to carry out multilevel regulations. In given synthetic circuits, drugs often act as inputs to drive circuits operation.

Tumor-Associated Macrophages: Recent Insights and Therapies.

Macrophages, which have functions of engulfing and digesting foreign substances, can clear away harmful matter, including cellular debris and tumor cells. Based on the condition of the internal environment, circulating monocytes give rise to mature macrophages, and when they are recruited into the tumor microenvironment and in suitable conditions, they are converted into tumor-associated macrophages (TAMs). Generally, macrophages grow into two main groups called classically activated macrophages (M1) and alternatively activated macrophages (M2).

Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription.

Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.

Design, synthesis and biological evaluation of a novel tubulin inhibitor SKLB0565 targeting the colchicine binding site.

A series of 3-(((9H-purin-6-yl) amino) methyl) pyridin-2(1H)-one derivatives were designed, synthesized and confirmed as tubulin polymerization inhibitors. All compounds were evaluated for their anti-proliferative activities on three colorectal carcinoma (CRC) cell lines. Among these compounds, SKLB0565 displayed noteworthy potency against eight CRC cell lines with IC values ranging from 0.

Potential effects of antibiotic-induced gut microbiome alteration on blood-brain barrier permeability compromise in rhesus monkeys.

The blood-brain barrier (BBB) contributes to the maintenance of brain homeostasis. Gut microbiome composition affects BBB development and expression of tight junction proteins in rodents. However, we still do not know if there is any direct effect of gut microbial composition on BBB permeability and function in normal adult animals.

Tumor Targeted Curcumin Delivery by Folate-Modified MPEG-PCL Self-Assembly Micelles for Colorectal Cancer Therapy.

Introduction: Curcumin (Cur) is a natural extract of Asian spice , showing multi-targeting capability and low toxicity in anti-tumor activities. The low bioavailability restricts its application as a therapeutic agent. Folate (FA) receptors are highly expressed in many malignant tumors while low expressed in normal tissue.

Rhynchophylline Loaded-mPEG-PLGA Nanoparticles Coated with Tween-80 for Preliminary Study in Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is a growing concern in the modern society. The current drugs approved by FDA are not very promising. Rhynchophylline (RIN) is a major active tetracyclic oxindole alkaloid stem from traditional Chinese medicine uncaria species, which has potential activities beneficial for the treatment of AD.

A mutation-independent CRISPR-Cas9-mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder associated with high mortality. Although a promising treatment for late-onset OTC deficiency, adeno-associated virus (AAV) neonatal gene therapy would only provide short-term therapeutic effects as the non-integrated genome gets lost during hepatocyte proliferation. CRISPR-Cas9-mediated homology-directed repair can correct a G-to-A mutation in 10% of OTC alleles in the livers of newborn OTC mice.

Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors.

Protein kinase inhibitors and epigenetic regulatory molecules are two main kinds of anticancer drugs developed in recent years. Both kinds of drugs harbor their own advantages and disadvantages in the treatment of cancer, and the development of small molecules which could target at kinases and epigenetic targets simultaneously can avoid the defects of drugs which only targets at kinases or epigenetic proteins. In this study, a series of 4,5-dihydro-[1,2,4]triazolo [4,3-f]pteridine derivatives were designed and synthesized based on the structure of PLK1 inhibitor BI-2536.

Inhibition Mechanism of Indoleamine 2, 3-Dioxygenase 1 (IDO1) by Amidoxime Derivatives and Its Revelation in Drug Design: Comparative Molecular Dynamics Simulations.

For cancer treatment, in addition to the three standard therapies of surgery, chemotherapy, and radiotherapy, immunotherapy has become the fourth internationally-recognized alternative treatment. Indoleamine 2, 3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan to kynurenine causing lysine depletion, which is an important target in the research and development of anticancer drugs. Epacadostat (INCB024360) is currently one of the most potent IDO1 inhibitors, nevertheless its inhibition mechanism still remains elusive.

Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation.

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation.

Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals.

MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC).

Identification of Interferon Receptor IFNAR2 As a Novel HCV Entry Factor by Using Chemical Probes.

Upon sensing pathogen-associated patterns and secreting interferons (IFNs) into the environment, host cells perceive extracellular type I IFNs by the IFNα/β receptors IFNAR1 and IFNAR2 to stimulate downstream innate immune signaling cascades. Through the use of chemical probes, we demonstrated that IFNAR2 facilitates hepatitis C virus (HCV) entry. Silencing of IFNAR2 significantly attenuated HCV proliferation.

Endothelial Autophagy: an Effective Target for Radiation-induced Cerebral Capillary Damage.

Toxicity to central nervous system tissues is the common side effects for radiotherapy of brain tumor. The radiation toxicity has been thought to be related to the damage of cerebral endothelium. However, because of lacking a suitable high-resolution vivo model, cellular response of cerebral capillaries to radiation remained unclear.

CD4 T-Cell Differentiation In Vitro.

CD4 T helper cells play crucial roles in adaptive immune response against pathogens, as well as in host immune homeostasis. Upon TCR activation, naïve CD4 T cells differentiate into one of several lineages of Th cells, with hallmark transcription factors, cytokine production, and functions in vivo, according to the particular cytokine milieu. To study the regulating mechanism and function of Th cells, in vitro CD4 T-cell differentiation is crucial.

Ability of Radiomics in Differentiation of Anaplastic Oligodendroglioma From Atypical Low-Grade Oligodendroglioma Using Machine-Learning Approach.

To investigate the ability of radiomics features from MRI in differentiating anaplastic oligodendroglioma (AO) from atypical low-grade oligodendroglioma using machine-learning algorithms. A total number of 101 qualified patients (50 participants with AO and 51 with atypical low-grade oligodendroglioma) were enrolled in this retrospective, single-center study. Forty radiomics features of tumor images derived from six matrices were extracted from contrast-enhanced T1-weighted (T1C) images and fluid-attenuation inversion recovery (FLAIR) images.

Bacterial particles retard tumor growth as a novel vascular disrupting agent.

Due to hypoxia and poor circulation in the tumor interior, malignant cells in solid tumors are resistant to traditional therapies. In the present study, we reported that bacterial particles (BactPs) functioned effectively in retarding tumor growth as a novel vascular disrupting agent. The BactPs were inactivated intact bacteria.

IL-18R-dependent and independent pathways account for IL-18-enhanced antitumor ability of CAR-T cells.

Interleukin-18 (IL-18) has been demonstrated to augment the antitumor capacity of chimeric antigen receptor-T cells (CAR-T) but the underlying mechanisms are largely unknown. Here we explored the effects and mechanisms of exogenous IL-18 on the antitumor response of CAR-T cells. IL-18 boosted the cytotoxicity of human epidermal growth factor receptor-2 (HER2)-specific CAR-T cells ex vivo and enhanced the antitumor efficacy of the CAR-T cells in immunodeficient mice, moreover, IL-18 improved the antitumor capacity of OVA-specific T cells in immunocompetent mice, indicating the universal enhancing function of IL-18 for adoptive cell therapy.

A potential target for liver cancer management, lysophosphatidic acid receptor 6 (LPAR6), is transcriptionally up-regulated by the NCOA3 coactivator.

Lysophosphatidic acid receptor 6 (LPAR6) is a G protein-coupled receptor that plays critical roles in cellular morphology and hair growth. Although LPAR6 overexpression is also critical for cancer cell proliferation, its role in liver cancer tumorigenesis and the underlying mechanism are poorly understood. Here, using liver cancer and matched paracancerous tissues, as well as functional assays including cell proliferation, quantitative real-time PCR, RNA-Seq, and ChIP assays, we report that LPAR6 expression is controlled by a mechanism whereby hepatocyte growth factor (HGF) suppresses liver cancer growth.

Correction: Loss of augments the regeneration of nervous lateral line system through negative regulation of transcription.

[This corrects the article DOI: 10.18632/oncotarget.11895.

Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists.

A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC = 4.9 nM) and 37 (EC = 8.