476,255 results match your criteria Cell death & disease[Journal]


Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells.

Oral Dis 2020 Jul 12. Epub 2020 Jul 12.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China.

Objective: There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anticancer effect of isorhamnetin.

Methods And Materials: OSCC cells were treated with or without isorhamnetin. Read More

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http://dx.doi.org/10.1111/odi.13548DOI Listing

Necrotic cell death increases the release of Macrophage migration inhibitory factor (MIF) by monocytes/macrophages.

Immunol Cell Biol 2020 Jul 12. Epub 2020 Jul 12.

Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.

Macrophage migration inhibitory factor is a pleiotropic inflammatory molecule with both cytokine and non-cytokine activity. MIF is constitutively released from multiple cell types via an unconventional secretory pathway that is not well defined. Here, we looked at MIF release from human and mouse monocytes/macrophages in response to different stimuli. Read More

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http://dx.doi.org/10.1111/imcb.12376DOI Listing

Metabolic Epilepsies Amenable to Ketogenic Therapies: Indications, Contra-indications and Underlying Mechanisms.

J Inherit Metab Dis 2020 Jul 12. Epub 2020 Jul 12.

Departments of Neurosciences & Pediatrics, University of California San Diego, Rady Children's Hospital, California, USA.

Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS), Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency, Pyruvate Dehydrogenase Complex (PDHC) Deficiency, Non-Ketotic Hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. Read More

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http://dx.doi.org/10.1002/jimd.12283DOI Listing

Inhibition of autophagy by chloroquine enhances the antitumor activity of gemcitabine for gallbladder cancer.

Cancer Chemother Pharmacol 2020 Jul 11. Epub 2020 Jul 11.

Department of Surgery, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, 200065, People's Republic of China.

Gemcitabine (GEM), as an anti-metabolic nucleoside analog, has been shown to have anticancer effects in various tumors, but its chemotherapy resistance is still an important factor leading to poor prognosis of cancer patient. A large number of studies in recent years have shown that autophagy plays an important role in the chemotherapy sensitivity of many tumors, including pancreatic, non-small cell lung, and bladder cancer. However, whether GEM causes autophagy in gallbladder cancer (GBC) and whether it is related to chemotherapy resistance is unknown. Read More

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http://dx.doi.org/10.1007/s00280-020-04100-5DOI Listing

Formulation of Stattic as STAT3 inhibitor in nanostructured lipid carriers (NLCs) enhances efficacy of doxorubicin in melanoma cancer cells.

Naunyn Schmiedebergs Arch Pharmacol 2020 Jul 11. Epub 2020 Jul 11.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

Nowadays, nanoparticle-based combination therapy has been emerging as huge innovation in cancer treatment. Here, we studied the effect of Stattic (STAT3 inhibitor) loaded in nanostructured lipid carriers (NLCs) on enhancing the efficacy, cytotoxicity, and induction of apoptosis of doxorubicin in B16F10 mouse melanoma cancer cell. The evaluation of Stattic-loaded NLCs has been done in terms of zeta potential, particle size, scanning electron microscope (SEM), and cellular uptake. Read More

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http://dx.doi.org/10.1007/s00210-020-01942-xDOI Listing

Mitochondria in acute myocardial infarction and cardioprotection.

EBioMedicine 2020 Jul 9;57:102884. Epub 2020 Jul 9.

National Heart Research Institute Singapore, National Heart Centre, Singapore; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore; Department of Biochemistry, Medical Faculty, Justus Liebig-University, Giessen, Germany; Yong Loo Lin School of Medicine, National University Singapore, Singapore; The Hatter Cardiovascular Institute, University College London, London, UK; Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taiwan. Electronic address:

Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such, new treatments are needed to protect the myocardium against the damaging effects of the acute ischaemia and reperfusion injury (IRI) that occurs in AMI, in order to reduce myocardial infarct (MI) size, preserve cardiac function, and improve patient outcomes. In this regard, cardiac mitochondria play a dual role as arbiters of cell survival and death following AMI. Read More

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http://dx.doi.org/10.1016/j.ebiom.2020.102884DOI Listing

Deep tissue volumetric optoacoustic tracking of individual circulating tumor cells in an intracardially perfused mouse model.

Neoplasia 2020 Jul 9;22(9):441-446. Epub 2020 Jul 9.

Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, University of Zurich and ETH Zurich, Switzerland; Institute of Biological and Medical Imaging (IBMI), Technical University of Munich and Helmholtz Center Munich, Germany.

Widespread metastasis is the major cause of death from melanoma and other types of cancer. At present, the dynamic aspects of the metastatic cascade remain enigmatic. The feasibility to track circulating melanoma cells deep within living intact organisms can greatly impact our knowledge on tumor metastasis, but existing imaging approaches lack the sensitivity, spatio-temporal resolution or penetration depth to capture flowing tumor cells over large fields of view within optically-opaque biological tissues. Read More

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http://dx.doi.org/10.1016/j.neo.2020.06.008DOI Listing

Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? A multicentre retrospective study.

Eur J Cancer 2020 Jul 9;136:76-83. Epub 2020 Jul 9.

Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address:

Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC. Read More

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http://dx.doi.org/10.1016/j.ejca.2020.02.019DOI Listing

Differential lethal action of C17:2 and C17:0 anacardic acid derivatives in Trypanosoma cruzi - A mechanistic study.

Bioorg Chem 2020 Jul 2;102:104068. Epub 2020 Jul 2.

Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP 09210-180, Brazil. Electronic address:

The n-hexane extract from leaves of Schinus terebinthifolius (Anacardiaceae) induced 100% of death of trypomastigote forms of T. cruzi at 300 μg/mL and was subjected to a bioactivity-guided fractionation to afford a C17:2 derivative of anacardic acid [6-(8'Z,11'Z)-heptadecadienyl-salicylic acid, 1]. Additionally, compound 1 was subjected to hydrogenation procedures to afford a C17:0 derivative (6-heptadecanyl-salicylic acid, 1a). Read More

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http://dx.doi.org/10.1016/j.bioorg.2020.104068DOI Listing

A liposome-based cancer vaccine for a rapid and high-titre anti-ErbB-2 antibody response.

Eur J Pharm Sci 2020 Jul 9:105456. Epub 2020 Jul 9.

Institute of Biomedical Engineering, University of Oxford, UK. Electronic address:

Vaccines are arguably the most important medical technology developed to date. However, effective treatment of diseases such as breast cancer have so far evaded standard vaccination strategies. One popular target for cancer treatment is the cell surface membrane protein, ErbB-2, also known as Her-2 or neu. Read More

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http://dx.doi.org/10.1016/j.ejps.2020.105456DOI Listing

The new role of FF ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection.

Exp Neurol 2020 Jul 9:113400. Epub 2020 Jul 9.

Section of Endocrinology, Department of Internal Medicine, Yale University, New Haven, CT, USA.

The mitochondrial FF ATP synthase is one of the most abundant proteins of the mitochondrial inner membrane, which catalyzes the final step of oxidative phosphorylation to synthesize ATP from ADP and Pi. ATP synthase uses the electrochemical gradient of protons (Δμ) across the mitochondrial inner membrane to synthesize ATP. Under certain pathophysiological conditions, ATP synthase can run in reverse to hydrolyze ATP and build the necessary Δμ across the mitochondrial inner membrane. Read More

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http://dx.doi.org/10.1016/j.expneurol.2020.113400DOI Listing

Association of Extended Dosing Intervals or Delays in Pembrolizumab-based Regimens With Survival Outcomes in Advanced Non-small-cell Lung Cancer.

Clin Lung Cancer 2020 Jun 5. Epub 2020 Jun 5.

Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address:

Background: Besides modeling/simulation-based analysis, no post-approval studies have evaluated the optimal administration frequency of pembrolizumab in non-small-cell lung cancer (NSCLC).

Patients And Methods: We performed a multicenter retrospective cohort study to evaluate the association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in patients with advanced NSCLC. Those who had received at least 4 cycles in routine practice were divided into 2 groups: nonstandard (Non-Std, ≥ 2 cycles at intervals > 3 weeks + 3 days) and standard (Std, all cycles every 3 weeks or 1 cycle > 3 weeks + 3 days). Read More

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http://dx.doi.org/10.1016/j.cllc.2020.05.028DOI Listing

Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy.

J Hematol Oncol 2020 Jul 11;13(1):89. Epub 2020 Jul 11.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Background: The oncolytic viruses have shown promising results for the treatment of multiple myeloma. However, the use of human viruses is limited by the patients' antiviral immune response. In this study, we investigated an alternative oncolytic strategy using non-human pathogen viruses as the bovine viral diarrhea virus (BVDV) that were able to interact with CD46. Read More

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http://dx.doi.org/10.1186/s13045-020-00919-wDOI Listing

Higher sensitivity of female cells to ethanol: methylation of DNA lowers Cyp2e1, generating more ROS.

Cell Commun Signal 2020 Jul 11;18(1):111. Epub 2020 Jul 11.

Queens College and Graduate Center, City University of New York, 65-30 Kissena Blvd, NSB E143, Flushing, NY, 11367, USA.

Background: Cells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol.

Methods: We evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states. Read More

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http://dx.doi.org/10.1186/s12964-020-00616-8DOI Listing

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia.

Part Fibre Toxicol 2020 Jul 11;17(1):30. Epub 2020 Jul 11.

Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing, 210009, P. R. China.

Background: Graphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation. Read More

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http://dx.doi.org/10.1186/s12989-020-00363-1DOI Listing

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report.

BMC Gastroenterol 2020 Jul 11;20(1):220. Epub 2020 Jul 11.

Department of Surgery, Shizuoka City Shimizu Hospital, 1231 Miyakami, Shimizu-ku, Shizuoka, 424-8636, Japan.

Background: Therapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined. Read More

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http://dx.doi.org/10.1186/s12876-020-01362-4DOI Listing

Ageing-associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca homeostasis and promotes cardiac dysfunction.

J Cell Mol Med 2020 Jul 11. Epub 2020 Jul 11.

Departments of Biophysics, Ankara University Faculty of Medicine, Ankara, Turkey.

The prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age-associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co-transporter gene (SGLT2) in disrupted cellular Ca -homeostasis, and mitochondrial dysfunction in age-associated cardiac dysfunction. In contrast to younger rats (6-month of age), older rats (24-month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities. Read More

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http://dx.doi.org/10.1111/jcmm.15483DOI Listing

Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke.

Glia 2020 Jul 11. Epub 2020 Jul 11.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Air Force Military Medical University, Xi'an, China.

Brain edema is a grave complication of brain ischemia and is the main cause of herniation and death. Although astrocytic swelling is the main contributor to cytotoxic edema, the molecular mechanism involved in this process remains elusive. N-myc downstream-regulated gene 2 (NDRG2), a well-studied tumor suppressor gene, is mainly expressed in astrocytes in mammalian brains. Read More

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http://dx.doi.org/10.1002/glia.23888DOI Listing

Mouse Double Minute 2 Amplification in Esophageal Squamous Cell Carcinoma Associated with Better Outcome.

Histopathology 2020 Jul 11. Epub 2020 Jul 11.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.

Aims: This study aimed to determine the frequency of mouse double minute 2 (MDM2) amplification in esophageal squamous cell carcinomas (ESCC) and to clarify its prognostic significance.

Methods: We investigated MDM2 amplification on tissue microarrays, using fluorescence in situ hybridization and analyzed its correlations with clinicopathological features and outcomes in 515 Chinese ESCC patients.

Results: MDM2 amplifications were found in 37 of 515 ESCC patients (7. Read More

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http://dx.doi.org/10.1111/his.14208DOI Listing

Effects of short- and long-term exposure to cadmium on salivary glands and fat body of soil centipede Lithobius forficatus (Myriapoda, Chilopoda): Histology and ultrastructure.

Micron 2020 Jun 30;137:102915. Epub 2020 Jun 30.

Silesian University of Technology, Faculty of Automatic Control, Electronics and Computer Science, Akademicka 16, 44-100, Gliwice, Poland; Silesian University of Technology, Biotechnology Centre, Krzywoustego 8, 44-100, Gliwice, Poland.

Cadmium (Cd) is the most widely studied heavy metal in terms of food-chain accumulation and contamination because it can strongly affect all environments (e.g., soil, water, air). Read More

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http://dx.doi.org/10.1016/j.micron.2020.102915DOI Listing

Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer.

Transl Oncol 2020 Jul 8;13(10):100828. Epub 2020 Jul 8.

Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, 1161 21(st) Avenue South, Medical Center North, R0102, Nashville, TN 37232, United States; Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, 1161 21st Avenue South, Medical Center North, R0102, Nashville, TN 37232, United States; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Medical Center North, Nashville, TN 37232, United States; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, TN 37232, United States. Electronic address:

Improving response to epidermal growth factor receptor (EGFR)-targeted therapies in patients with advanced wild-type (WT) RAS colorectal cancer (CRC) remains an unmet need. In this preclinical work, we evaluated a new therapeutic combination aimed at enhancing efficacy by targeting cancer cell metabolism in concert with EGFR. We hypothesized that combined blockade of glutamine metabolism and EGFR represents a promising treatment approach by targeting both the "fuel" and "signaling" components that these tumors need to survive. Read More

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http://dx.doi.org/10.1016/j.tranon.2020.100828DOI Listing

CpG-coated Prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma.

Transl Oncol 2020 Jul 8;13(10):100823. Epub 2020 Jul 8.

The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA; The Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA; Department of Medicine, The George Washington University, Washington, DC 20037, USA. Electronic address:

High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a "nanoimmunotherapy," which combines photothermal therapy (PTT) using CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) combined with anti-CTLA-4 (aCTLA-4) immunotherapy. Our in vitro studies demonstrate that in addition to causing ablative tumor cell death, our nanoimmunotherapy alters the surface levels of co-stimulatory, antigen-presenting, and co-inhibitory molecules on neuroblastoma tumor cells. Read More

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http://dx.doi.org/10.1016/j.tranon.2020.100823DOI Listing

Quantifying DNA damage induced by ionizing radiation and hyperthermia using single DNA molecule imaging.

Transl Oncol 2020 Jul 8;13(10):100822. Epub 2020 Jul 8.

Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden. Electronic address:

Ionizing radiation (IR) is a common mode of cancer therapy, where DNA damage is the major reason of cell death. Here, we use an assay based on fluorescence imaging of single damaged DNA molecules isolated from radiated lymphocytes, to quantify IR induced DNA damage. The assay uses a cocktail of DNA-repair enzymes that recognizes and excises DNA lesions and then a polymerase and a ligase incorporate fluorescent nucleotides at the damage sites, resulting in a fluorescent "spot" at each site. Read More

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http://dx.doi.org/10.1016/j.tranon.2020.100822DOI Listing

Pathogenesis of Alzheimer's disease: Multiple interacting causes against which amyloid precursor protein protects.

Med Hypotheses 2020 Jun 25;143:110035. Epub 2020 Jun 25.

Garburn House, Westmorland General Hospital, Burton Road, Kendal, Cumbria LA9 7RG, UK.

Alzheimer's disease is the commonest form of senile dementia. It is characterised by neuronal cell death and amyloid deposition. Amyloid precursor protein (APP), which is highly conserved in evolution, is expressed in neurones in response to a wide range of damaging agents. Read More

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http://dx.doi.org/10.1016/j.mehy.2020.110035DOI Listing

Pembrolizumab-induced severe oral mucositis in a patient with squamous cell carcinoma of the lung: A case study.

Lung Cancer 2020 Jun 30;147:21-25. Epub 2020 Jun 30.

Division of Medical Oncology-Hematology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

Background: Immune checkpoint inhibitors, such as pembrolizumab, a humanized monoclonal antibody against programmed death-1, elicit antitumor activity in various types of cancers, including lung cancer. However, pembrolizumab has been reported to cause diverse immune-related adverse events associated with T-cell activation.

Case Presentation: We present the case of a 61-year-old man with advanced non-small cell lung cancer who was administered pembrolizumab as first-line treatment. Read More

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http://dx.doi.org/10.1016/j.lungcan.2020.06.033DOI Listing

The Regulatory and Enzymatic Functions of CRMPs in Neuritogenesis, Synaptic Plasticity, and Gene Transcription.

Authors:
Sheng Tao Hou

Neurochem Int 2020 Jul 8:104795. Epub 2020 Jul 8.

Brain Research Centre and Department of Biology, Southern University of Science and Technology, 1088 Xueyuan Blvd, Nanshan District, Shenzhen, Guangdong Province, PR China, 518055; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address:

Collapsin response mediator proteins (CRMPs) are ubiquitously expressed in neurons from worms to humans. A cardinal feature of CRMPs is to mediate growth cone collapse in response to Semaphorin-3A signaling through interactions with cytoskeletal proteins. These are critical regulatory roles that CRMPs play during neuritogenesis and neural network formation. Read More

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http://dx.doi.org/10.1016/j.neuint.2020.104795DOI Listing

Development, evaluation and effect of anionic co-ligand on the biological activity of benzothiazole derived copper(II) complexes.

J Inorg Biochem 2020 Jul 3;210:111174. Epub 2020 Jul 3.

Department of Chemistry, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, District Ajmer, Rajasthan 305817, India. Electronic address:

Research on development of novel metal based anti-cancer agents continues with its popularity among bioinorganic community. Benzothiazole, an important heterocyclic pharmacophore, was chosen as a valuable and useful scaffold for the synthesis of novel copper(II) complexes. Three new copper(II) complexes obtained from the synthesis of newly synthesized benzothiazole based N-(benzo[d]thiazol-2-ylmethyl)-N-methyl-2-(pyridin-2-yl)ethan-1-amine (btzpy) ligand with CuCl [Cu(btzpy)Cl] (1), Cu(NCS) [Cu(btzpy)(NCS)] (2), and Cu(NO) [Cu(btzpy)(NO)(HO)]NO (3) were isolated and characterized by physical and spectroscopic measurements, including single-crystal X-ray structures. Read More

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http://dx.doi.org/10.1016/j.jinorgbio.2020.111174DOI Listing

Osimertinib improves overall survival in EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastases regardless of T790M mutational status.

J Thorac Oncol 2020 Jul 8. Epub 2020 Jul 8.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address:

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), efficiently penetrates the blood-brain barrier. Current study explored whether treatment with osimertinib leads to improved overall survival (OS) for EGFR-mutated NSCLC patients with leptomeningeal metastases (LM) compared with those not treated with osimertinib.

Methods: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. Read More

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http://dx.doi.org/10.1016/j.jtho.2020.06.018DOI Listing

In vivo assessment of cell death and nigrostriatal pathway integrity following continuous expression of C3 transferase.

Neuroscience 2020 Jul 8. Epub 2020 Jul 8.

Department of Neurosurgery, United States. Electronic address:

The bacterial exoenzyme C3 transferase (C3) irreversibly inhibits RhoA GTPase leading to stimulation of axonal outgrowth in injured neurons. C3 has been used successfully in models of neurotrauma and shows promise as an option to support cell survival and axonal growth of dopaminergic neurons in Parkinson's disease cell therapy. Whether the continuous expression of C3 in dopaminergic neurons is well-tolerated is unknown. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2020.07.006DOI Listing

An analysis of mitotic catastrophe induced cell responses in melanoma cells exposed to flubendazole.

Authors:
K Rudolf E Rudolf

Toxicol In Vitro 2020 Jul 8:104930. Epub 2020 Jul 8.

Department of Medical Biology and Genetics, Charles University, Faculty of Medicine in Hradec Králové, Czech Republic. Electronic address:

Mitotic catastrophe induced by mictotubule-targeting drugs such as benzimidazole carbamates has been demonstrated to be an efficient mechanism for suppression of tumor cells growth and proliferation, with variable resulting endpoints. The present study was designed to explore some of these endpoints; i.e. Read More

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http://dx.doi.org/10.1016/j.tiv.2020.104930DOI Listing

Evaluation of the ameliorative effects of oral administration of metformin on epileptogenesis in the temporal lobe epilepsy model in rats.

Life Sci 2020 Jul 8:118066. Epub 2020 Jul 8.

Cellular and Molecular Research Center and Department of Physiology, School of Medicine Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: Understanding the underlying molecular mechanisms involved in epileptogenesis is necessary to target the best therapeutic interventions in epilepsy. Recently, it has been postulated that metformin, an old antidiabetic oral drug, has anti-seizure properties mostly due to its antioxidant activities. This study was designed to evaluate the ameliorative effects of metformin on the progression of epilepsy in the temporal lobe epilepsy model in rats. Read More

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http://dx.doi.org/10.1016/j.lfs.2020.118066DOI Listing

Dietary Lipids Induce Ferroptosis in Caenorhabditiselegans and Human Cancer Cells.

Dev Cell 2020 Jun 30. Epub 2020 Jun 30.

School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA, USA. Electronic address:

Dietary lipids impact development, homeostasis, and disease, but links between specific dietary fats and cell fates are poorly understood. Ferroptosis is an iron-dependent form of nonapoptotic cell death associated with oxidized polyunsaturated phospholipids. Here, we show that dietary ingestion of the polyunsaturated fatty acid (PUFA) dihomogamma-linolenic acid (DGLA; 20:3n-6) can trigger germ-cell ferroptosis and sterility in the nematode Caenorhabditis elegans. Read More

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http://dx.doi.org/10.1016/j.devcel.2020.06.019DOI Listing

Tumor Organoids to Study Gastroesophageal Cancer: A Primer.

J Mol Cell Biol 2020 Jul 11. Epub 2020 Jul 11.

Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. Read More

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http://dx.doi.org/10.1093/jmcb/mjaa035DOI Listing

Optogenetic Downregulation of Protein Levels to Control Programmed Cell Death in Mammalian Cells with a Dual Blue-Light Switch.

Methods Mol Biol 2020 ;2173:159-170

Institute of Synthetic Biology, University of Düsseldorf, Düsseldorf, Germany.

Optogenetic approaches facilitate the study of signaling and metabolic pathways in animal cell systems. In the past 10 years, a plethora of light-regulated switches for the targeted control over the induction of gene expression, subcellular localization of proteins, membrane receptor activity, and other cellular processes have been developed and successfully implemented. However, only a few tools have been engineered toward the quantitative and spatiotemporally resolved downregulation of proteins. Read More

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http://dx.doi.org/10.1007/978-1-0716-0755-8_11DOI Listing
January 2020

AKI: an increasingly recognized risk factor for CKD development and progression.

J Nephrol 2020 Jul 10. Epub 2020 Jul 10.

Division of Nephrology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Ross 965, 720 Rutland Ave, Baltimore, MD, 21206, USA.

Acute kidney injury (AKI) is an increasing health burden with high morbidity and mortality rates worldwide. AKI is a risk factor for chronic kidney disease (CKD) development and progression to end stage renal disease (ESRD). Rapid action is required to find treatment options for AKI, plus to anticipate the development of CKD and other complications. Read More

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http://dx.doi.org/10.1007/s40620-020-00793-2DOI Listing

Anti-transcriptional intermediary factor 1-γ antibody-positive dermatomyositis induced by nivolumab for lung adenocarcinoma: A case report.

Invest New Drugs 2020 Jul 10. Epub 2020 Jul 10.

Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.

Immune checkpoint inhibitors can induce immune-related adverse events (irAEs) in different organs. Dermatomyositis is a rare form of systemic irAE. Although dermatomyositis-specific antibodies, especially anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibodies, have been detected in a few cases of immune checkpoint inhibitor-associated dermatomyositis, their titers before immunotherapy have not been examined. Read More

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http://dx.doi.org/10.1007/s10637-020-00974-7DOI Listing

Bassoon inhibits proteasome activity via interaction with PSMB4.

Cell Mol Life Sci 2020 Jul 10. Epub 2020 Jul 10.

Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.

Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Read More

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http://dx.doi.org/10.1007/s00018-020-03590-zDOI Listing

Cell death in the gut epithelium and implications for chronic inflammation.

Nat Rev Gastroenterol Hepatol 2020 Jul 10. Epub 2020 Jul 10.

Department of Medicine 1, Friedrich-Alexander University, Erlangen, Germany.

The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate ~300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Read More

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http://dx.doi.org/10.1038/s41575-020-0326-4DOI Listing

Pan-RAF inhibition induces apoptosis in acute myeloid leukemia cells and synergizes with BCL2 inhibition.

Leukemia 2020 Jul 10. Epub 2020 Jul 10.

Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

Pan-RAF inhibitors have shown promise as antitumor agents in RAS and RAF mutated solid cancers. However, the efficacy of pan-RAF inhibitors in acute myeloid leukemia (AML) has not previously been explored. In AML, the RAS-RAF-MEK-ERK (MAPK) pathway is one of the most aberrantly activated oncogenic pathways, but previous targeting of this pathway by MEK inhibitors has not proven effective in clinical trials. Read More

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http://dx.doi.org/10.1038/s41375-020-0972-0DOI Listing

Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1.

Cell Death Dis 2020 Jul 10;11(7):522. Epub 2020 Jul 10.

Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, PR China.

Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. Read More

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http://dx.doi.org/10.1038/s41419-020-2729-0DOI Listing

Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer's Disease in 3×Tg-AD Model Mice.

J Alzheimers Dis 2020 Jul 9. Epub 2020 Jul 9.

Laboratory of Neurodegenerative Diseases, chool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.

Background: The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs.

Objective: We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-β (Aβ) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function. Read More

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http://dx.doi.org/10.3233/JAD-200257DOI Listing

Nitrogen trapping as a therapeutic strategy in tumors with mitochondrial dysfunction.

Cancer Res 2020 Jul 10. Epub 2020 Jul 10.

Medicine, Massachusetts General Hospitals

Under conditions of inherent or induced mitochondrial dysfunction, cancer cells manifest overlapping metabolic phenotypes, suggesting that they may be targeted via a common approach. Here we use multiple oxidative phosphorylation (OXPHOS)-competent and -incompetent cancer cell pairs to demonstrate that treatment with alpha-ketoglutarate (aKG) esters elicits rapid death of OXPHOS-deficient cancer cells by elevating intracellular aKG concentrations, thereby sequestering nitrogen from aspartate through glutamic-oxaloacetic transaminase 1 (GOT1). Exhaustion of aspartate in these cells resulted in immediate depletion of adenylates, which plays a central role in mediating mTOR inactivation and inhibition of glycolysis. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-0246DOI Listing

Clinical safety profile of transendocardial catheter injection systems: A plea for uniform reporting.

Cardiovasc Revasc Med 2020 Jun 30. Epub 2020 Jun 30.

Division of Cardiovascular Medicine, University of Florida, Gainsville, FL, USA.

Objectives: The aim of this study was to characterize the clinical safety profile of transendocardial injection catheters (TIC) reported in the published literature.

Background: Transendocardial delivery is a minimally invasive approach to deliver potential therapeutic agents directly into the myocardium. The rate of adverse events across TIC is uncertain. Read More

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http://dx.doi.org/10.1016/j.carrev.2020.06.031DOI Listing

Investigating proteome changes between primary and metastatic cutaneous squamous cell carcinoma using SWATH mass spectrometry.

J Dermatol Sci 2020 Jun 30. Epub 2020 Jun 30.

Centre for Translational Skin Research, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia; Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia. Electronic address:

Background: Cutaneous squamous cell carcinoma (cSCC) is a common malignancy worldwide and the first as the cause of death from keratinocytic carcinomas. Around 5% of primary cSCCs metastasize, leading to a 5-year survival rate of only 11 %.

Objective: This paper aims to investigate the proteome profile of primary and metastatic cSCC lesions for the identification of potential diagnostic biomarkers and molecular alterations. Read More

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http://dx.doi.org/10.1016/j.jdermsci.2020.06.012DOI Listing

Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) ganglion induced by chronic sleep deprivation, in the rat model.

Biol Res 2020 Jul 10;53(1):31. Epub 2020 Jul 10.

Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. Read More

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http://dx.doi.org/10.1186/s40659-020-00300-8DOI Listing

Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma.

Orphanet J Rare Dis 2020 Jul 10;15(1):183. Epub 2020 Jul 10.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease; Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510120, China.

Objective: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. Read More

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http://dx.doi.org/10.1186/s13023-020-01449-xDOI Listing

Addressing advanced HIV disease and mortality in global HIV programming.

AIDS Res Ther 2020 Jul 10;17(1):40. Epub 2020 Jul 10.

Division of Global HIV and TB, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road NE, US 1-1, Atlanta, GA, 30329, USA.

Introduction: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. Read More

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http://dx.doi.org/10.1186/s12981-020-00296-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348123PMC

Prion peptide-mediated calcium level alteration governs neuronal cell damage through AMPK-autophagy flux.

Cell Commun Signal 2020 Jul 11;18(1):109. Epub 2020 Jul 11.

Biosafety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Gobong ro, Iksan, Jeonbuk, 54596, South Korea.

Background: The distinctive molecular structure of the prion protein, PrPsc, is established only in mammals with infectious prion diseases. Prion protein characterizes either the transmissible pathogen itself or a primary constituent of the disease. Our report suggested that prion protein-mediated neuronal cell death is triggered by the autophagy flux. Read More

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http://dx.doi.org/10.1186/s12964-020-00590-1DOI Listing

Conditioning regimen intensity and low-dose azacitidine maintenance after allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

Leuk Lymphoma 2020 Jul 10:1-11. Epub 2020 Jul 10.

Department of Blood and Marrow Transplant, AdventHealth Hospital, Orlando, FL, USA.

Azacitidine (AZA) maintenance following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may reduce relapse risk and improve survival. Given logistic and toxicity-related challenges, identifying subgroups appropriate for this approach is an unmet need. Using data from two centers, we retrospectively compared event-free survival (EFS) and overall survival (OS) of AML and MDS patients who received AZA maintenance ( = 59) with historic controls ( = 90). Read More

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http://dx.doi.org/10.1080/10428194.2020.1789630DOI Listing

Cancer Associated Endogenous Retroviruses: Ideal Immune Targets for Adenovirus-Based Immunotherapy.

Int J Mol Sci 2020 Jul 8;21(14). Epub 2020 Jul 8.

InProTher, Bioinnovation Institute, Copenhagen Bio Science Park, 2200 Copenhagen, Denmark.

Cancer is a major challenge in our societies, according to the World Health Organization (WHO) about 1/6 deaths were cancer related in 2018 and it is considered the second leading cause of death globally. Immunotherapies have changed the paradigm of oncologic treatment for several cancers where the field had fallen short in providing competent therapies. Despite the improvement, broadly acting and highly effective therapies capable of eliminating or preventing human cancers with insufficient mutated antigens are still missing. Read More

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http://dx.doi.org/10.3390/ijms21144843DOI Listing