129,416 results match your criteria cells suppression


Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Cell Chem Biol 2021 May 7. Epub 2021 May 7.

Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address:

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Read More

View Article and Full-Text PDF

Phragmunis A suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Neurochem Int 2021 May 9:105051. Epub 2021 May 9.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China. Electronic address:

Glioblastoma (GBM) is a highly aggressive brain tumour. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Read More

View Article and Full-Text PDF

Deletion of in Preosteoblasts Reveals a Role for the Mammalian Target of Rapamycin Complex 1 (mTORC1) Complex in Dietary-Induced Changes to Bone Mass and Glucose Homeostasis in Female Mice.

JBMR Plus 2021 May 24;5(5):e10486. Epub 2021 Mar 24.

Adelaide Medical School, Faculty of Health and Medical Science University of Adelaide Adelaide South Australia Australia.

The mammalian target of rapamycin complex 1 (mTORC1) complex is the major nutrient sensor in mammalian cells that responds to amino acids, energy levels, growth factors, and hormones, such as insulin, to control anabolic and catabolic processes. We have recently shown that suppression of the mTORC1 complex in bone-forming osteoblasts (OBs) improved glucose handling in male mice fed a normal or obesogenic diet. Mechanistically, this occurs, at least in part, by increasing OB insulin sensitivity leading to upregulation of glucose uptake and glycolysis. Read More

View Article and Full-Text PDF

Removal of CD276 cells from haploidentical memory T-cell grafts significantly lowers the risk of GVHD.

Bone Marrow Transplant 2021 May 11. Epub 2021 May 11.

Department of Hematology and Oncology, Children's Hospital, Universität Tübingen, Tübingen, Germany.

Detrimental graft-versus-host disease (GVHD) still remains a major cause of death in hematopoietic stem cell transplantation (HSCT). The recently explored depletion of naive cells from mobilized grafts (CD45RA depletion) has shown considerable promise, yet is unable to eliminate the incidence of GVHD. Analysis of CD45RA-depleted haploidentical mixed lymphocytes culture (haplo-MLC) revealed insufficient suppression of alloresponses in the CD4 compartment and identified CD276 as a marker for alloreactive memory Th1 T cells. Read More

View Article and Full-Text PDF

Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer.

Nat Commun 2021 May 11;12(1):2699. Epub 2021 May 11.

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. Read More

View Article and Full-Text PDF

Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas.

Nat Commun 2021 May 11;12(1):2582. Epub 2021 May 11.

Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA, USA.

Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma (GBM) trials. Here, we show that regulatory T (Treg) cells play a key role in GBM resistance to ICBs in experimental gliomas. Targeting glucocorticoid-induced TNFR-related receptor (GITR) in Treg cells using an agonistic antibody (αGITR) promotes CD4 Treg cell differentiation into CD4 effector T cells, alleviates Treg cell-mediated suppression of anti-tumor immune response, and induces potent anti-tumor effector cells in GBM. Read More

View Article and Full-Text PDF

Knockout RAGE alleviates cardiac fibrosis through repressing endothelial-to-mesenchymal transition (EndMT) mediated by autophagy.

Cell Death Dis 2021 May 11;12(5):470. Epub 2021 May 11.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. Read More

View Article and Full-Text PDF

The SARS-CoV-2 Transcriptome and the Dynamics of the S Gene Furin Cleavage Site in Primary Human Airway Epithelia.

mBio 2021 May 11;12(3). Epub 2021 May 11.

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA

The spike (S) polypeptide of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary that contains a furin cleavage site (FCS), RRAR↓S Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, it acquired deletions surrounding the FCS. We studied the viral transcriptome in Vero cell-derived SARS-CoV-2-infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability of the FCS. Read More

View Article and Full-Text PDF

Suppression of ACADM-mediated fatty acid oxidation promotes hepatocellular carcinoma via aberrant Cav1/SREBP-1 signaling.

Cancer Res 2021 May 11. Epub 2021 May 11.

Department of Pathology, University of Hong Kong

Lipid accumulation exacerbates tumor development, as it fuels the proliferative growth of cancer cells. The role of medium-chain acyl-CoA dehydrogenase (ACADM), an enzyme that catalyses the first step of mitochondrial fatty acid oxidation, in tumor biology remains elusive. Therefore, investigating its mode of dysregulation can shed light on metabolic dependencies in cancer development. Read More

View Article and Full-Text PDF

The MNK1/2-eIF4E axis supports immune suppression and metastasis in postpartum breast cancer.

Cancer Res 2021 May 11. Epub 2021 May 11.

Goodman Cancer Research Center, McGill University.

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment has not been explored. Read More

View Article and Full-Text PDF

Meis homeobox 2 (MEIS2) inhibits the proliferation and promotes apoptosis of thyroid cancer cell and through the NF-κB signaling pathway.

Bioengineered 2021 Dec;12(1):1766-1772

Department of Otolaryngology Head and Neck Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Investigation of effects of Meis homeobox 2 (MEIS2) on proliferation and apoptosis of thyroid cancer (TC) cells and its specific molecular mechanism is the main purpose of this study. In this study, we found that the expression of MEIS2 was down-regulated in TC tissues and cell lines (B-CPAP, TPC-1 and K1), compared to adjacent histologically normal tissues and normal thyroid cell (Nthy-ori 3-1). Then, overexpression of MEIS2 promoted B-CPAP cell apoptosis and decreased cell proliferation, viability and cell cycle progression. Read More

View Article and Full-Text PDF
December 2021

Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.

Transpl Immunol 2021 May 8:101405. Epub 2021 May 8.

Department of Biofunctional Microbiota, Juntendo University Graduate School of Medicine, Tokyo, Japan; Division of Cell Biology, Biomedical Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address:

Background: Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model.

Methods: We analyzed the effects of induced syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) on graft survival and suppressive capacity. Read More

View Article and Full-Text PDF

Novel hyaluronic acid oligosaccharide-loaded and CD44v6-targeting oxaliplatin nanoparticles for the treatment of colorectal cancer.

Drug Deliv 2021 Dec;28(1):920-929

Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, PR China.

Oxaliplatin resistance is one of the main causes of failed colorectal cancer treatment, followed by recurrence and metastasis. In this study, we found that colorectal cancer cells secrete a high level of hyaluronic acid (HA), which interacts with its receptor CD44v6 to mediate colorectal cancer resistance to chemotherapy. HA oligosaccharide (oHA) is a degradation product of HA. Read More

View Article and Full-Text PDF
December 2021

G2 and S phase-expressed-1 acts as a putative tumor promoter in cervical cancer by enhancing Wnt/β-catenin signaling via modulation of GSK-3β.

Environ Toxicol 2021 May 11. Epub 2021 May 11.

Department of Physiology and Pathophysiology, Air Force Medical University, Xi'an, China.

G2 and S phase-expressed-1 (GTSE1) is currently identified as a key regulator of carcinogenesis. However, the involvement of GTSE1 in cervical cancer is unclear. The aims of this work were to explore the relationship between GTSE1 and cervical cancer. Read More

View Article and Full-Text PDF

Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity.

Authors:
Brian A Baldo

Arch Toxicol 2021 May 11. Epub 2021 May 11.

Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, Sydney, NSW, 2070, Australia.

Opioid-induced respiratory depression is potentially life-threatening and often regarded as the main hazard of opioid use. Main cause of death is cardiorespiratory arrest with hypoxia and hypercapnia. Respiratory depression is mediated by opioid μ receptors expressed on respiratory neurons in the CNS. Read More

View Article and Full-Text PDF

LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy.

J Exp Med 2021 Jul 11;218(7). Epub 2021 May 11.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Read More

View Article and Full-Text PDF

Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based first-line regimen: a prospective cohort study.

AIDS 2021 May 10. Epub 2021 May 10.

Médecins Sans Frontières South Africa Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa University of Cape Town, Cape Town, South Africa University of Liverpool, Department of Pharmacology, Liverpool, United Kingdom Division of Public Health Medicine, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa University of Stellenbosch, Division of Medical Virology, Cape Town, South Africa Department of Medicine, University of Cape Town, Cape Town, South Africa Department of Infectious Disease, Imperial College London, London, UK.

Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine.

Design: Single arm, prospective, interventional study. Read More

View Article and Full-Text PDF

Limited inhibition of multiple nodes in a driver network blocks metastasis.

Elife 2021 May 11;10. Epub 2021 May 11.

Ben May Department for Cancer Research, University of Chicago, Chicago, United States.

Metastasis suppression by high-dose, multi-drug targeting is unsuccessful due to network heterogeneity and compensatory network activation. Here we show that targeting driver network signaling capacity by limited inhibition of core pathways is a more effective anti-metastatic strategy. This principle underlies the action of a physiological metastasis suppressor, Raf Kinase Inhibitory Protein (RKIP), that moderately decreases stress-regulated MAP kinase network activity, reducing output to transcription factors such as pro-metastastic BACH1 and motility-related target genes. Read More

View Article and Full-Text PDF

Methylmercury induces neuronal cell death by inducing TNF-α expression through the ASK1/p38 signaling pathway in microglia.

Sci Rep 2021 May 10;11(1):9832. Epub 2021 May 10.

Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aoba-ku, Aramaki, Sendai, Miyagi, 980-8578, Japan.

We recently found that tumor necrosis factor-α (TNF-α) may be involved in neuronal cell death induced by methylmercury in the mouse brain. Here, we examined the cells involved in the induction of TNF-α expression by methylmercury in the mouse brain by in situ hybridization. TNF-α-expressing cells were found throughout the brain and were identified as microglia by immunostaining for ionized calcium binding adaptor molecule 1 (Iba1). Read More

View Article and Full-Text PDF

Suppression of Cancer-associated bone loss through dynamic mechanical loading.

Bone 2021 May 7:115998. Epub 2021 May 7.

Stony Brook University, Department of Biomedical Engineering, Stony Brook, NY, USA.

Patients afflicted with or being treated for cancer constitute a distinct and alarming subpopulation who exhibit elevated fracture risk and heightened susceptibility to developing secondary osteoporosis. Cancer cells uncouple the regulatory processes central for the adequate regulation of musculoskeletal tissue. Systemically taxing treatments to target tumors or disrupt the molecular elements driving tumor growth place considerable strain on recovery efforts. Read More

View Article and Full-Text PDF

Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells.

Am J Respir Cell Mol Biol 2021 May 10. Epub 2021 May 10.

Thomas Jefferson University, 6559, Philadelphia, Pennsylvania, United States;

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, are not completely elucidated. Read More

View Article and Full-Text PDF

Usnic acid suppresses cervical cancer cell proliferation by inhibiting PD-L1 expression and enhancing T-lymphocyte tumor-killing activity.

Phytother Res 2021 May 10. Epub 2021 May 10.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. Read More

View Article and Full-Text PDF

Peroxiredoxin 5 is involved in cancer cell invasion and tumor growth of oral squamous cell carcinoma.

Oral Dis 2021 May 9. Epub 2021 May 9.

Department of Dental Hygiene, College of Health Science, Eulji University, 13135, Republic of Korea.

Objectives: Peroxiredoxins (Prxs) are antioxidant enzymes that can coordinate cell signal transduction via reactive species scavenging or by acting as redox sensors. The mechanism by which Prxs promote cancer invasion and progression is not yet fully understood. This study aims to elucidate the precise mechanism through which Prx type 5 (Prx5) promotes cancer invasion and tumor growth. Read More

View Article and Full-Text PDF

Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics.

Lancet Microbe 2021 May 4;2(5):e210-e218. Epub 2021 Mar 4.

Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: The COVID-19 agent, SARS-CoV-2, is conspecific with SARS-CoV, the causal agent of the severe acute respiratory syndrome epidemic in 2002-03. Although the viruses share a completely homologous repertoire of proteins and use the same cellular entry receptor, their transmission efficiencies and pathogenetic traits differ. We aimed to compare interferon antagonism by SARS-CoV and SARS-CoV-2. Read More

View Article and Full-Text PDF

Long Non-Coding RNA LINC01929 Accelerates Progression of Oral Squamous Cell Carcinoma by Targeting the miR-137-3p/FOXC1 Axis.

Front Oncol 2021 21;11:657876. Epub 2021 Apr 21.

Department of General Dentistry, Hospital of Stomatology, Jilin University, Changchun, China.

Recently, additional long noncoding RNAs (lncRNAs) have been identified and their possible roles were investigated in a variety of human tumors. One of these lncRNAs, LINC01929, promoted the progression of some cancers, whereas its expression and biological function in human oral squamous cell carcinoma (OSCC) remains still mostly uncertain. The LINC01929 expression in OSCC tissues or cell lines was identified quantitative real-time polymerase chain reaction. Read More

View Article and Full-Text PDF

miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5.

Front Oncol 2021 23;11:600451. Epub 2021 Apr 23.

Department of Neurosurgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. Read More

View Article and Full-Text PDF

Ulinastatin Ameliorates IL-1-Induced Cell Dysfunction in Human Nucleus Pulposus Cells via Nrf2/NF-B Pathway.

Oxid Med Cell Longev 2021 21;2021:5558687. Epub 2021 Apr 21.

Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University (Second Military Medical University), No. 415 Fengyang Road, Shanghai 200003, China.

Low back pain (LBP) has been a wide public health concern worldwide. Among the pathogenic factors, intervertebral disc degeneration (IDD) has been one of the primary contributors to LBP. IDD correlates closely with inflammatory response and oxidative stress, involving a variety of inflammation-related cytokines, such as interleukin 1 beta (IL-1), which could result in local inflammatory environment. Read More

View Article and Full-Text PDF

MicroRNA-219a-2-3p modulates the proliferation of thyroid cancer cells via the HPSE/cyclin D1 pathway.

Exp Ther Med 2021 Jun 20;21(6):659. Epub 2021 Apr 20.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Heparanase (HPSE) is an endo-β-D-glucuronidase overexpressed in different types of human cancer, and a predicted target of microRNA (miRNA/miR)-219a-2-3p in thyroid cancer. The present study aimed to investigate the potential role of HPSE and miR-219a-2-3p in thyroid cancer, and the molecular mechanism of miR-219a-2-3p regulating the proliferation of thyroid cancer cells via HPSE was confirmed. Immunohistochemistry analysis was performed to detect HPSE expression in thyroid cancer sections. Read More

View Article and Full-Text PDF

Oxidative Stress-Mediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris.

Front Immunol 2021 19;12:649502. Epub 2021 Apr 19.

Centre for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, London, United Kingdom.

(PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). Read More

View Article and Full-Text PDF

Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer.

Front Immunol 2021 23;12:643771. Epub 2021 Apr 23.

Breast Tumor Immunology Laboratory, Dana-Farber Cancer Institute, Boston, MA, United States.

Macrophages are crucial innate immune cells that maintain tissue homeostasis and defend against pathogens; however, their infiltration into tumors has been associated with adverse outcomes. Tumor-associated macrophages (TAMs) represent a significant component of the inflammatory infiltrate in breast tumors, and extensive infiltration of TAMs has been linked to poor prognosis in breast cancer. Here, we detail how TAMs impede a productive tumor immunity cycle by limiting antigen presentation and reducing activation of cytotoxic T lymphocytes (CTLs) while simultaneously supporting tumor cell survival, angiogenesis, and metastasis. Read More

View Article and Full-Text PDF