10,699 results match your criteria Ataxia-Telangiectasia


The paradigm of hematological malignant versus non-malignant manifestations, driven by primary immunodeficiencies: a complex interplay.

Fam Cancer 2021 Jun 15. Epub 2021 Jun 15.

Department of Pediatric Hematology-Oncology, "Aghia Sophia" Children's Hospital, Thivon 1 & Papadiamantopoulou, 11527, Athens, Greece.

Hematological malignancies (HM) developed on underlying primary immunodeficiencies (PID) are rare and of unusual features. Differentiating between malignant and non-malignant lymphoproliferation in cases of pediatric hematology and oncology and revealing their molecular predisposition demonstrate the complex interplay between PID and HM. We retrospectively studied a case series of seven pediatric patients, all with PID with manifestations raising suspicion for HM or hypereosinophilic syndrome (HES) or confirmed HM of lymphoid origin. Read More

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Sensors and Inhibitors for the Detection of Ataxia Telangiectasia Mutated (ATM) Protein Kinase.

Mol Pharm 2021 Jun 14. Epub 2021 Jun 14.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States.

Recruitment and activation of the ataxia telangiectasia mutated (ATM) kinase regulate multiple cell-cycle checkpoints relevant to complex biological events like DNA damage repair and apoptosis. Molecularly specific readouts of ATM using protein assays, fluorescence, or radiolabeling have advanced significantly over the past few years. This Review covers the molecular imaging techniques that enable the visualization of ATM-from traditional quantitative protein assays to the potential use of ATM inhibitors to generate new imaging agents to interrogate ATM. Read More

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First international workshop of the ATM and cancer risk group (4-5 December 2019).

Fam Cancer 2021 Jun 14. Epub 2021 Jun 14.

Huntsman Cancer Institute, Salt Lake City, USA.

The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. Read More

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Mutant Single Nucleotide Polymorphism rs189037 in Ataxia-Telangiectasia Mutated Gene Is Significantly Associated With Ventricular Wall Thickness and Human Lifespan.

Front Cardiovasc Med 2021 26;8:658908. Epub 2021 May 26.

Central Laboratory, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China.

In the current study, we aimed to determine the association of single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated () gene with cardiac structure and human longevity. Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan Province, China, the current study enrolled 547 centenarians, 250 young participants aged 20-45 years, and 250 middle-aged and elderly participants aged 46-90 years. The frequency of TT genotype was significantly higher and that of CC genotype was significantly lower in middle-aged and elderly participants than in young ( = 0. Read More

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Loss of ATRX confers DNA repair defects and PARP inhibitor sensitivity.

Transl Oncol 2021 Jun 9;14(9):101147. Epub 2021 Jun 9.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA. Electronic address:

Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) is mutated frequently in gliomas and represents a potential target for cancer therapies. ATRX is known to function as a histone chaperone that helps incorporate histone variant, H3.3, into the genome. Read More

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Immunological abnormalities in patients with early-onset ataxia with ocular motor apraxia and hypoalbuminemia.

Clin Immunol 2021 Jun 9:108776. Epub 2021 Jun 9.

Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. Read More

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Evaluating causality of cellular senescence in non-alcoholic fatty liver disease.

JHEP Rep 2021 Aug 1;3(4):100301. Epub 2021 May 1.

Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.

Cellular senescence is a state of irreversible cell cycle arrest that has important physiological functions. However, cellular senescence is also a hallmark of ageing and has been associated with several pathological conditions. A wide range of factors including genotoxic stress, mitogens and inflammatory cytokines can induce senescence. Read More

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GPR68 Contributes to Persistent Acidosis-Induced Activation of AGC Kinases and Tyrosine Phosphorylation in Organotypic Hippocampal Slices.

Front Neurosci 2021 25;15:692217. Epub 2021 May 25.

Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL, United States.

Persistent acidosis occurs in ischemia and multiple neurological diseases. In previous studies, acidic stimulation leads to rapid increase in intracellular calcium in neurons. However, it remains largely unclear how a prolonged acidosis alters neuronal signaling. Read More

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Modulation of DNA damage response by targeting ATM kinase using newly synthesized di-phenoxy acetamide (DPA) analogs to induce anti-neoplasia.

Pharmacol Rep 2021 Jun 9. Epub 2021 Jun 9.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, India.

Background: Imbalance and instability in the structure of the DNA have become major characteristics of cancer. In response to DNA damage, DNA damage response (DDR) protein, ataxia telangiectasia mutated (ATM), plays a pivotal role in the modulation of regulatory regions responsible for inhibition of apoptosis, thereby neoplastic progression.

Methods: A new series of DPA (7a-t) were synthesized, characterized. Read More

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Effectiveness of Physiotherapy on Ataxia-Telangiectasia: A Case Report.

Pediatr Phys Ther 2021 Jun 7. Epub 2021 Jun 7.

Faculty of Physical Therapy and Rehabilitation (Mr Unes, Ms Tuncdemir, and Dr Kerem Gunel), Hacettepe University, Ankara, Turkey; Department of Pediatric Neurology (Dr Eroglu-Ertugrul), Faculty of Medicine, Hacettepe University, Turkey.

Background And Purpose: This case report investigated the benefits of a 12-week physical therapy program for a child with ataxia-telangiectasia (AT).

Case Description: A 9-year-old girl with a diagnosis of AT participated. The physical therapy program consisted of balance and strength exercise and Wii Fit Balance-based video games training with a pediatric physical therapist for 12 weeks. Read More

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AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.

Front Oncol 2021 20;11:680663. Epub 2021 May 20.

Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. Read More

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Maize ATR Safeguards Genome Stability During Kernel Development to Prevent Early Endosperm Endocycle Onset and Cell Death.

Plant Cell 2021 Jun 4. Epub 2021 Jun 4.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, B-9052, Belgium.

The Ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) kinases coordinate the DNA damage response (DDR). The roles described for Arabidopsis thaliana ATR and ATM are assumed to be conserved over other plant species, but molecular evidence is scarce. Here, we demonstrate that the functions of ATR and ATM are only partially conserved between Arabidopsis and maize (Zea mays). Read More

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Molecular and Radiological Features of Microsatellite Stable Colorectal Cancer Cases With Dramatic Responses to Immunotherapy.

Anticancer Res 2021 Jun;41(6):2985-2992

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, U.S.A.;

Background/aim: The majority of colorectal cancer (CRC) cases, which are microsatellite stable (MSS) and do not harbor mismatch repair deficiency/microsatellite instability, are resistant to immunotherapy. Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed.

Case Report: We report three cases of MSS CRC with durable clinical benefit from immunotherapy with anti-PD-1 checkpoint inhibitors. Read More

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SOG1 transcription factor promotes the onset of endoreduplication under salinity stress in Arabidopsis.

Sci Rep 2021 Jun 2;11(1):11659. Epub 2021 Jun 2.

Department of Botany, UGC Center for Advanced Studies, The University of Burdwan, Golapbag Campus, Burdwan, West Bengal, 713 104, India.

As like in mammalian system, the DNA damage responsive cell cycle checkpoint functions play crucial role for maintenance of genome stability in plants through repairing of damages in DNA and induction of programmed cell death or endoreduplication by extensive regulation of progression of cell cycle. ATM and ATR (ATAXIA-TELANGIECTASIA-MUTATED and -RAD3-RELATED) function as sensor kinases and play key role in the transmission of DNA damage signals to the downstream components of cell cycle regulatory network. The plant-specific NAC domain family transcription factor SOG1 (SUPPRESSOR OF GAMMA RESPONSE 1) plays crucial role in transducing signals from both ATM and ATR in presence of double strand breaks (DSBs) in the genome and found to play crucial role in the regulation of key genes involved in cell cycle progression, DNA damage repair, endoreduplication and programmed cell death. Read More

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Correction to: Neurofilament Light Chain is a Biomarker of Neurodegeneration in Ataxia Telangiectasia.

Cerebellum 2021 Jun 2. Epub 2021 Jun 2.

Division of Allergology, Pulmonology and Cystic Fibrosis, Department for Children and Adolescents, Goethe University, Frankfurt, Germany.

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SETD2-mediated H3K14 trimethylation promotes ATR activation and stalled replication fork restart in response to DNA replication stress.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, 518055 Shenzhen, China;

Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including replication protein A (RPA) complex loading onto single-stranded DNA and ATR activator loading onto chromatin. The contribution of histone modifications to ATR activation, however, is unclear. Here, we report that H3K14 trimethylation responds to replication stress by enhancing ATR activation. Read More

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Correction to: Growth in ataxia telangiectasia.

Orphanet J Rare Dis 2021 Jun 1;16(1):248. Epub 2021 Jun 1.

Division of Pediatric Allergy and Immunology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

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Silencing PEX26 as an Unconventional Mode to Kill Drug-Resistant Cancer Cells and Forestall Drug Resistance.

Autophagy 2021 Jun 1. Epub 2021 Jun 1.

Lady Davis Institute, McGill University, Montréal, Canada.

Promoting the macroautophagy/autophagy-mediated degradation of specific proteins and organelles can potentially be utilized to induce apoptosis in cancer cells or sensitize tumor cells to therapy. To examine this concept, we enriched for autophagosomes from histone deacetylase inhibitor (HDACi)-sensitive U937 lymphoma cells and isogenic HDACi-resistant cells. Mass spectrometry on autophagosome-enriched fractions revealed that HDACi-resistant cells undergo elevated pexophagy, or autophagy of the peroxisome, an organelle that supports tumor growth. Read More

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Circulating Tumor DNA Testing for Homology Recombination Repair Genes in Prostate Cancer: From the Lab to the Clinic.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Section of Pathological Anatomy, School of Medicine, Polytechnic University of the Marche Region, United Hospitals, 60126 Ancona, Italy.

Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes. Peripheral blood samples are typically used for the germline mutation analysis test using the DNA extracted from peripheral blood leucocytes. Read More

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The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice.

Genes (Basel) 2021 May 13;12(5). Epub 2021 May 13.

Division of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', A.O.U. Consorziale Policlinico di Bari, 70121 Bari, Italy.

Molecular alterations of the Ataxia-telangiectasia () gene are frequently detected in breast cancer (BC), with an incidence ranging up to 40%. The mutated form, the Ataxia-telangiectasia mutated () gene, is involved in cell cycle control, apoptosis, oxidative stress, and telomere maintenance, and its role as a risk factor for cancer development is well established. Recent studies have confirmed that some variants of are associated with an increased risk of BC development and a worse prognosis. Read More

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Upregulation of Chemoresistance by Mg Deficiency through Elevation of ATP Binding Cassette Subfamily B Member 1 Expression in Human Lung Adenocarcinoma A549 Cells.

Cells 2021 May 12;10(5). Epub 2021 May 12.

Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, Japan.

Several anticancer drugs including cisplatin (CDDP) induce hypomagnesemia. However, it remains fully uncertain whether Mg deficiency affects chemosensitivity of cancer cells. Here, we investigated the effect of low Mg concentration (LM) on proliferation and chemosensitivity using human lung adenocarcinoma A549 cells. Read More

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The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia.

Viruses 2021 May 9;13(5). Epub 2021 May 9.

Department of Pediatric Infectious Diseases, La Paz University Hospital, 28046 Madrid, Spain.

Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied.

Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses' polymerase chain reaction were collected monthly, and between visits in case of symptoms. Read More

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Circadian Rhythm of NER and ATR Pathways.

Authors:
Tae-Hong Kang

Biomolecules 2021 May 11;11(5). Epub 2021 May 11.

Department of Biomedical Sciences, Dong-A University, Busan 49315, Korea.

Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell cycle checkpoint, and apoptosis, are believed to be evolved to limit genomic instability according to the photoperiod during a day. As seen in many other key cellular metabolisms, genome surveillance mechanisms against genotoxic UV radiation are under the control of circadian clock systems, thereby exhibiting daily oscillations in their catalytic activities. Read More

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The PTEN and ATM axis controls the G1/S cell cycle checkpoint and tumorigenesis in HER2-positive breast cancer.

Cell Death Differ 2021 May 31. Epub 2021 May 31.

Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, ON, M5G 2C1, Canada.

The tumor suppressor PTEN is disrupted in a large proportion of cancers, including in HER2-positive breast cancer, where its loss is associated with resistance to therapy. Upon genotoxic stress, ataxia telangiectasia mutated (ATM) is activated and phosphorylates PTEN on residue 398. To elucidate the physiological role of this molecular event, we generated and analyzed knock-in mice expressing a mutant form of PTEN that cannot be phosphorylated by ATM (PTEN-398A). Read More

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The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation.

Front Cell Dev Biol 2021 12;9:650819. Epub 2021 May 12.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

This study aimed to investigate the effect of ataxia telangiectasia mutated (ATM)-mediated autophagy on the radiosensitivity of lung cancer cells under low-dose radiation and to further investigate the role of ATM and its specific mechanism in the transition from hyper-radiosensitivity (HRS) to induced radioresistance (IRR). The changes in the HRS/IRR phenomenon in A549 and H460 cells were verified by colony formation assay. Changes to ATM phosphorylation and cell autophagy in A549 and H460 cells under different low doses of radiation were examined by western blot, polymerase chain reaction (PCR), and electron microscopy. Read More

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Bavachinin Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Small Cell Lung Cancer and Shows an Antitumor Effect in the Xenograft Model.

J Agric Food Chem 2021 Jun 27;69(22):6260-6270. Epub 2021 May 27.

Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Huanggang Normal University, Huanggang 438000, Hubei Province, China.

Lung cancer is grouped into small cell lung cancer (SCLC) and non-SCLC (NSCLC). SCLC exhibits a poor prognosis, and the current anticancer treatment remains unsatisfactory. Bavachinin, present in the seed of , shows anti-inflammatory effects, immune modulation, and anticancer potency. Read More

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Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours.

Br J Cancer 2021 May 26. Epub 2021 May 26.

Translational and Clinical Research Institute, Newcastle University and Northern Centre for Cancer Care, Newcastle Hospitals NHS Trust, Newcastle Upon Tyne, UK.

Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours.

Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. Read More

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Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours.

Br J Cancer 2021 May 26. Epub 2021 May 26.

Drug Development Unit, Royal Marsden Hospital and The Institute of Cancer Research, London, UK.

Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. We assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of berzosertib plus cisplatin.

Methods: Adult patients with advanced solid tumours refractory or resistant to standard of care therapies received ascending doses of cisplatin (day 1) and berzosertib (days 2 and 9) every 3 weeks (Q3W). Read More

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Targeting IDH1/2 mutant cancers with combinations of ATR and PARP inhibitors.

NAR Cancer 2021 Jun 17;3(2):zcab018. Epub 2021 May 17.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA.

Mutations in the isocitrate dehydrogenase-1 and -2 (IDH1/2) genes were first identified in glioma and acute myeloid leukemia (AML), and subsequently found in multiple other tumor types. These neomorphic mutations convert the normal product of enzyme, α-ketoglutarate (αKG), to the oncometabolite 2-hydroxyglutarate (2HG). Our group recently demonstrated that 2HG suppresses the high-fidelity homologous recombination (HR) DNA repair pathway, resulting in a state referred to as 'BRCAness', which confers exquisite sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Read More

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Targeting DNA Damage Repair for Immune Checkpoint Inhibition: Mechanisms and Potential Clinical Applications.

Front Oncol 2021 7;11:648687. Epub 2021 May 7.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

DNA damage repair (DDR) pathways play an essential role in maintaining genomic integrity. DDR dysfunction leads to accumulated DNA damage, predisposition to cancer, and high sensitivity to chemotherapy and radiotherapy. Recent studies have demonstrated that DDR status is associated with response to immune checkpoint inhibitors (ICIs). Read More

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