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Chem Commun (Camb) 2021 Apr 19. Epub 2021 Apr 19.

IMGENEX INDIA Pvt. Ltd E-5, Infocity, Bhubaneswar, Odisha-751024, India.

An oxo(corrolato)chromium(v) complex selectively kills leukemia cells. However, this complex did not induce cell death in primary non-cancer cells. It has been observed that oxo(corrolato)chromium(v) complex induced cell death is associated with DNA damage. Read More

Mol Ther Oncolytics 2021 Jun 17;21:37-46. Epub 2021 Mar 17.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Oncolytic virotherapy holds promise of effective immunotherapy against otherwise nonresponsive cancers such as glioblastoma. Our previous findings have shown that although oncolytic Semliki Forest virus (SFV) is effective against various mouse glioblastoma models, its therapeutic potency is hampered by type I interferon (IFN-I)-mediated antiviral signaling. In this study, we constructed a novel IFN-I-resistant SFV construct, SFV-AM6, and evaluated its therapeutic potency , , and in the IFN-I competent mouse GL261 glioma model. Read More

Front Plant Sci 2021 31;12:630311. Epub 2021 Mar 31.

College of Life Sciences, Henan Agricultural University, Zhengzhou, China.

We have previously demonstrated that General Control Non-derepressible 1 (AtGCN1) is essential for translation inhibition under cold stress through interacting with GCN2 to phosphorylate eukaryotic translation initiation factor 2 (eIF2). Here, we report that the flower time of the mutant is later than that of the wild type (WT), and some siliques of cannot develop and produce seeds. Total and polysomal RNA of and wild type (WT) after cold treatments were sequenced. Read More

Sci Adv 2021 Apr 16;7(16). Epub 2021 Apr 16.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Netrin-1, a family member of laminin-related secreted proteins, mediates axon guidance and cell migration during neural development. T835M mutation in netrin receptor UNC5C predisposes to the late-onset Alzheimer's disease (AD) and increases neuronal cell death. However, it remains unclear how this receptor is molecularly regulated in AD. Read More

Drug Resist Updat 2021 Mar 19;56:100762. Epub 2021 Mar 19.

The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel. Electronic address:

Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. Read More

Cell Death Dis 2021 Apr 14;12(4):402. Epub 2021 Apr 14.

Department of Physiology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410000, PR China.

Caspase-11, a cytosolic lipopolysaccharide (LPS) receptor, mediates lethal immune responses and coagulopathy in sepsis, a leading cause of death worldwide with limited therapeutic options. We previously showed that over-activation of caspase-11 is driven by hepatocyte-released high mobility group box 1 (HMGB1), which delivers extracellular LPS into the cytosol of host cells during sepsis. Using a phenotypic screening strategy with recombinant HMGB1 and peritoneal macrophages, we discovered that FeTPPS, a small molecule selectively inhibits HMGB1-mediated caspase-11 activation. Read More

Sci Transl Med 2021 04;13(589)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. Read More

J Nanobiotechnology 2021 Apr 13;19(1):102. Epub 2021 Apr 13.

Department of Pharmaceutical Technology and Chemistry, School of Pharmacy, University of Navarra, 31008, Pamplona, Navarra, Spain.

Background: The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (α-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has led to the search for rational combinations with other therapeutic agents such as Doxorubicin (Dox), which cytotoxicity involves an immune activation that may enhance ICI response. Therefore, this study aims to evaluate the combination of chemotherapy and ICI by developing Dox Immunoliposomes functionalized with monovalent-variable fragments (Fab') of α-PD-L1. Read More

Front Pharmacol 2021 25;12:560903. Epub 2021 Mar 25.

Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medical, Ningbo University, Ningbo, China.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, can selectively induce cancer cell death while sparing normal cells. However, the application of TRAIL-based antitumor therapies has been hindered due to drug resistance. Alternol is a new compound isolated from microbial fermentation that possesses antitumor activity in different tumors. Read More

Bioorg Chem 2021 Mar 29;111:104880. Epub 2021 Mar 29.

Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address:

There remains a critical need for more effective therapies for the treatment of castration-resistant prostate cancer (CRPC), which is the leading cause of death in patients with prostate cancer. In this study, a series of sanjuanolide derivatives were designed, synthesized and evaluated as potential anti-CRPC agents. Most of the compounds had excellent selectivity for CRPC cells with IC values < 20 µM. Read More

Cancer Immunol Immunother 2021 Apr 10. Epub 2021 Apr 10.

Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Madrid, Spain.

Background: Antibody-based therapies blocking the programmed cell death-1/ligand-1 (PD-1/PD-L1) axis have provided unprecedent clinical success in cancer treatment. Acquired resistance, however, frequently occurs, commonly associated with the upregulation of additional inhibitory molecules. Diacylglycerol kinase (DGK) α limits the extent of Ras activation in response to antigen recognition, and its upregulation facilitates hypofunctional, exhausted T cell states. Read More

J Immunother Cancer 2021 Apr;9(4)

Binhui Biopharmaceutical Co., Ltd, Wuhan, China.

Background: OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express granulocyte-macrophage colony-stimulating factor to enhance antitumor immune responses. We investigated the safety, tolerability and antitumor activity of OH2 as single agent or in combination with HX008, an anti-programmed cell death protein 1 antibody, in patients with advanced solid tumors.

Methods: In this multicenter, phase I/II trial, we enrolled patients with standard treatment-refractory advanced solid tumors who have injectable lesions. Read More

Cell Commun Signal 2021 Apr 8;19(1):44. Epub 2021 Apr 8.

International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.

Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. Read More

Biomaterials 2021 Apr 1;272:120791. Epub 2021 Apr 1.

KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea. Electronic address:

The effective chemotherapeutic drug, doxorubicin (DOX), elicits immunogenic cell death (ICD) and additional anticancer immune responses during chemotherapy. However, it also induces severe side effects and systemic immunosuppression, hampering its wide clinical application. Herein, we constructed cancer-activated DOX prodrug by conjugating the cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly, FRRG) to a doxorubicin (DOX), resulting in FRRG-DOX that self-assembled into cancer-activated DOX prodrug nanoparticles (CAP-NPs). Read More

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Stanford Cardiovascular Institute.

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation. Read More

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA

The anti-apoptotic protein BCL2 inhibits death of HIV-infected cells. Previously, we have shown that the BCL2 inhibitor venetoclax selectively kills acutely HIV-infected cells and reduces HIV DNA in latently infected CD4 T cells after reactivation with αCD3/αCD28. However, there is a need to identify a combination therapy with venetoclax and a clinically relevant latency reversal agent. Read More

Phytomedicine 2021 May 18;85:153551. Epub 2021 Mar 18.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. Electronic address:

Background: Triple-negative breast cancer (TNBC), lacking targeted therapies currently, is susceptible to ferroptosis, a recently defined form of cell death.

Purpose: To evaluate the anticancer activity of Shuganning injection (SGNI), a traditional Chinese patent medicine, on TNBC cells; To elucidate the mechanism of SGNI induced ferroptosis.

Methods: The anticancer activity of SGNI was examined via in vitro cell proliferation assays and in vivo xenograft growth assay. Read More

Nat Commun 2021 04 6;12(1):2048. Epub 2021 Apr 6.

Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany.

Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate cell death pathways prior to therapy. Yet, which of these pathways remain available in treatment-naïve SCLC is unknown. Here, through systemic analysis of cell death pathway availability in treatment-naïve SCLC, we identify non-neuroendocrine (NE) SCLC to be vulnerable to ferroptosis through subtype-specific lipidome remodeling. Read More

Evid Based Complement Alternat Med 2021 16;2021:6668665. Epub 2021 Mar 16.

College of Korean Medicine, Dongguk University, Goyang, Republic of Korea.

Objectives: Ginsenoside Rg3 (Rg3), a main active component of , has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes.

Methods: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. Read More

Int J Mol Sci 2021 Mar 31;22(7). Epub 2021 Mar 31.

School of Medicine, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR13SD, UK.

Cancer "stem cells" (CSCs) sustain the hierarchies of dividing cells that characterize cancer. The main causes of cancer-related mortality are metastatic disease and relapse, both of which originate primarily from CSCs, so their eradication may provide a bona fide curative strategy, though there maybe also the need to kill the bulk cancer cells. While classic anti-cancer chemotherapy is effective against the dividing progeny of CSCs, non-dividing or quiescent CSCs are often spared. Read More

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy.

CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. Read More

Materials (Basel) 2021 Mar 17;14(6). Epub 2021 Mar 17.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André 09210-580, SP, Brazil.

Holmium-containing bioactive glasses can be applied in bone cancer treatment because the holmium content can be neutron activated, having suitable properties for brachytherapy applications, while the bioactive glass matrix can regenerate the bone alterations induced by the tumor. To facilitate the application of these glasses in clinical practice, we proposed a composite based on Poloxamer 407 thermoresponsive hydrogel, with suitable properties for applications as injectable systems. Therefore, in this work, we evaluated the influence of holmium-containing glass particles on the properties of Poloxamer 407 hydrogel (20 /. Read More

Microorganisms 2021 Mar 10;9(3). Epub 2021 Mar 10.

The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea.

The structure-function relationships of toxin-antitoxin (TA) systems from have prompted the development of novel and effective antimicrobial agents that selectively target this organism. The artificial activation of toxins by peptide inhibitors can lead to the growth arrest and eventual death of bacterial cells. Optimizing candidate peptides by hydrocarbon α-helix stapling based on structural information from the VapBC TA system and in vitro systematic validation led to , a VapC26 activator of . Read More

Cancers (Basel) 2021 Mar 14;13(6). Epub 2021 Mar 14.

Research Institute of Medical & Health Sciences, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates.

The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins (BIM, BAD, NOXA, PUMA, BID, BIK, HRK). Notably, the BCL-2 antiapoptotic proteins are often overexpressed in malignant cells. Read More

Prog Chem Org Nat Prod 2021 ;115:59-114

Department of Oncology, Prostate Cancer Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Maryland, The Johns Hopkins University School of Medicine, Baltimore, The Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD, 21231, USA.

Thapsigargin, the first representative of the hexaoxygenated guaianolides, was isolated 40 years ago in order to understand the skin-irritant principles of the resin of the umbelliferous plant Thapsia garganica. The pronounced cytotoxicity of thapsigargin is caused by highly selective inhibition of the intracellular sarco-endoplasmic Ca-ATPase (SERCA) situated on the membrane of the endo- or sarcoplasmic reticulum. Thapsigargin is selective to the SERCA pump and to a minor extent the secretory pathway Ca/Mn ATPase (SPCA) pump. Read More

Trends Endocrinol Metab 2021 Mar 29. Epub 2021 Mar 29.

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address:

Targeting tumor cell metabolism is an attractive form of therapy, as it may enhance treatment response in therapy resistant cancers as well as mitigate treatment-related toxicities by reducing the need for genotoxic agents. To meet their increased demand for biomass accumulation and energy production and to maintain redox homeostasis, tumor cells undergo profound changes in their metabolism. In addition to the diversion of glucose metabolism, this is achieved by upregulation of amino acid metabolism. Read More

Int J Pharm 2021 Mar 29;601:120553. Epub 2021 Mar 29.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Pancreatic cancer (PC) is an aggressive form of cancer with dense stroma and immune-suppressive microenvironment, which are the major barriers for treatment. To address such barriers, this study aimed to develop a sequential receptor-mediated mixed-charge targeted delivery system for PC based on 2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate (ACUPA) and triphenylphosphonium (TPP) modified nanomicelles containing ingenol-3-mebutate (I3A), which was named ACUPA/TPP-I3A or ACUPA/TPP-I3A. ACUPA/TPP-I3A induced immunogenic cell death (ICD), which significantly increased the number of tumor-infiltrating T lymphocytes, activated adaptive immunity, and achieved superior survival time. Read More

Biomed Res Int 2021 17;2021:6697476. Epub 2021 Mar 17.

Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Jiangsu 226001, China.

Purpose: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and angiogenesis has been proven to be significantly involved in its progression. However, the molecular mechanism underlying HCC angiogenesis has not been well researched. In this study, RNA Binding Motif Protein 23 (RBM23) was identified as a novel proangiogenic factor in HCC cell lines and tissues. Read More

Front Mol Biosci 2021 10;8:628332. Epub 2021 Mar 10.

Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czechia.

TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL-based therapies in humans have certain limitations. Read More

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

State Key Laboratory of Medical Molecular Biology and Department of Medical Genetics, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.

Cancer cell-intrinsic programmed cell death protein-1 (PD-1) has emerged as a tumor regulator in an immunity-independent manner, but its precise role in modulating tumor behaviors is complex, and how PD-1 is regulated in cancer cells is largely unknown. Here, we identified PD-1 as a direct target of tumor suppressor p53. Notably, p53 acetylation at K120/164 played a critical role in p53-mediated PD-1 transcription. Read More