11,285 results match your criteria Ataxia-telangiectasia


Cell Fate following Irradiation of MDA-MB-231 and MCF-7 Breast Cancer Cells Pre-Exposed to the Tetrahydroisoquinoline Sulfamate Microtubule Disruptor STX3451.

Molecules 2022 Jun 14;27(12). Epub 2022 Jun 14.

Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.

A tetrahydroisoquinoline (THIQ) core is able to mimic the A and B rings of 2-methoxyestradiol (2ME2), an endogenous estrogen metabolite that demonstrates promising anticancer properties primarily by disrupting microtubule dynamic instability parameters, but has very poor pharmaceutical properties that can be improved by sulfamoylation. The non-steroidal THIQ-based microtubule disruptor 2-(3-bromo-4,5-dimethoxybenzyl)-7-methoxy-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (STX3451), with enhanced pharmacokinetic and pharmacodynamic profiles, was explored for the first time in radiation biology. We investigated whether 24 h pre-treatment with STX3451 could pre-sensitize MCF-7 and MDA-MB-231 breast cancer cells to radiation. Read More

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Non-Thermal Plasma Jet-Treated Medium Induces Selective Cytotoxicity against -Infected Macrophages.

Biomedicines 2022 May 26;10(6). Epub 2022 May 26.

Department of Microbiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.

Plasma-treated media (PTM) serve as an adjuvant therapy to postoperatively remove residual cancerous lesions. We speculated that PTM could selectively kill cells infected with () and remove postoperative residual tuberculous lesions. We therefore investigated the effects of a medium exposed to a non-thermal plasma jet on the suppression of intracellular replication, cell death, signaling, and selectivity. Read More

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Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India.

Sci Rep 2022 Jun 21;12(1):10416. Epub 2022 Jun 21.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency's and other disorders affecting different aspects of the immune system. Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. Read More

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ATM Modulates Nuclear Mechanics by Regulating Lamin A Levels.

Front Cell Dev Biol 2022 1;10:875132. Epub 2022 Jun 1.

Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, United States.

Ataxia-telangiectasia mutated (ATM) is one of the three main apical kinases at the crux of DNA damage response and repair in mammalian cells. ATM activates a cascade of downstream effector proteins to regulate DNA repair and cell cycle checkpoints in response to DNA double-strand breaks. While ATM is predominantly known for its role in DNA damage response and repair, new roles of ATM have recently begun to emerge, such as in regulating oxidative stress or metabolic pathways. Read More

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Case Report: Rubella Virus-Induced Cutaneous Granulomas in Two Pediatric Patients With DNA Double Strand Breakage Repair Disorders - Outcome After Hematopoietic Stem Cell Transplantation.

Front Immunol 2022 2;13:886540. Epub 2022 Jun 2.

Department of Pediatric Respiratory Medicine, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.

We report two patients with DNA repair disorders (Artemis deficiency, Ataxia telangiectasia) with destructive skin granulomas, presumably triggered by live-attenuated rubella vaccinations. Both patients showed reduced naïve T cells. Rapid resolution of skin lesions was observed following hematopoietic stem cell transplantation. Read More

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Spontaneous Regression of Diffuse Large B-cell Lymphoma in a Patient with Ataxia-Telangiectasia.

Adv Biomed Res 2022 29;11:31. Epub 2022 Apr 29.

Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Ataxia-telangiectasia (AT) is a type of primary immunodeficiency characterized by an autosomal recessive mode of inheritance and usually presents with progressive cerebellar ataxia in early life. This complex disease is associated with humoral and cellular immune dysfunction and other features including characteristic oculocutaneous telangiectasia and increased predisposition to cancers, particularly lymphoma and leukemia. An 11-year-old Iranian girl presented with primary immunodeficiency and was diagnosed as having AT according to her clinical manifestations and molecular findings. Read More

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A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells.

Front Oncol 2022 31;12:765968. Epub 2022 May 31.

Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Patients with human papillomavirus-positive squamous cell carcinoma of the head and neck (HPV+ HNSCC) have a favorable prognosis compared to those with HPV-negative (HPV-) ones. We have shown previously that HPV+ HNSCC cell lines are characterized by enhanced radiation sensitivity and impaired DNA double-strand break (DSB) repair. Since then, various publications have suggested a defect in homologous recombination (HR) and dysregulated expression of DSB repair proteins as underlying mechanisms, but conclusions were often based on very few cell lines. Read More

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Minigene-based splicing analysis and ACMG/AMP-based tentative classification of 56 ATM variants.

J Pathol 2022 Jun 18. Epub 2022 Jun 18.

Splicing and genetic susceptibility to cancer, Unidad de Excelencia Instituto de Biología y Genética Molecular. Consejo Superior de Investigaciones Científicas (CSIC-UVa), 47003, Valladolid, Spain.

The ataxia telangiectasia-mutated (ATM) protein is a major coordinator of the DNA damage response pathway. ATM loss-of-function variants are associated with two-fold increased breast cancer risk. We aimed at identifying and classifying spliceogenic ATM variants detected in subjects of the large-scale sequencing project BRIDGES. Read More

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Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer.

Breast Cancer Res 2022 Jun 17;24(1):41. Epub 2022 Jun 17.

Department of Obstetrics and Gynecology, University Hospital of Cologne, Kerpener Str. 34, 50931, Cologne, Germany.

Background: The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype.

Methods: Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. Read More

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Hallmarks of DNA replication stress.

Mol Cell 2022 Jun;82(12):2298-2314

Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address:

Faithful DNA replication is critical for the maintenance of genomic integrity. Although DNA replication machinery is highly accurate, the process of DNA replication is constantly challenged by DNA damage and other intrinsic and extrinsic stresses throughout the genome. A variety of cellular stresses interfering with DNA replication, which are collectively termed replication stress, pose a threat to genomic stability in both normal and cancer cells. Read More

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A Germline Mutation in ATR Is Associated With Lung Adenocarcinoma in Asian Patients.

Front Oncol 2022 31;12:855305. Epub 2022 May 31.

Department of Thoracic Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.

Background: Familial lung cancer (FLC) accounts for 8% of lung adenocarcinoma. It is known that a few germline mutations are associated with risk increasing and may provide new screening and treatment option. The goal of this study is to identify an FLC gene among three members of an FLC family. Read More

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The Application of ATR Kinase Inhibitor AZD6738 in Combination with Radiotherapy for the Treatment of Melanoma.

J Biomed Phys Eng 2022 Jun 1;12(3):267-276. Epub 2022 Jun 1.

MSc, Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background: Melanoma is categorized as one of the most malignant, severe, and lethal cancers of the skin. Regarding the lack of efficiency of conventional therapies for most patients, novel therapeutic strategies are strongly required.

Objective: The current study aimed to assess the impact of AZD6738- an ATR kinase inhibitor- in combination with 6 MV X-ray on the human melanoma cell line (A375). Read More

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Assessing the quantification of acetylation in konjac glucomannan via ATR-FTIR and solid-state NMR spectroscopy.

Carbohydr Polym 2022 Sep 26;291:119659. Epub 2022 May 26.

Western Sydney University, Australian Centre for Research on Separation Science (ACROSS), School of Science, Parramatta Campus, Locked Bag 1797, Penrith, NSW 2751, Australia. Electronic address:

Dietary fiber like konjac glucomannan (KGM) is important in maintaining good human health. There is no established method for quantifying the average degree of acetylation DA of this polysaccharide. Polysaccharides are notoriously difficult to dissolve. Read More

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September 2022

The ataxia-telangiectasia mutated gene product regulates the cellular acid-labile sulfide fraction.

DNA Repair (Amst) 2022 May 14;116:103344. Epub 2022 May 14.

Department of Pathology & Translational Pathobiology, LSU Health Sciences Center Shreveport, Shreveport, LA 71130, United States. Electronic address:

The ataxia-telangiectasia mutated (ATM) protein regulates cell cycle checkpoints, the cellular redox state, and double-stranded DNA break repair. ATM loss causes the disorder ataxia-telangiectasia (A-T), distinguished by ataxia, telangiectasias, dysregulated cellular redox and iron responses, and an increased cancer risk. We examined the sulfur pool in A-T cells, with and without an ATM expression vector. Read More

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ATR-mediated CD47 and PD-L1 up-regulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer.

Sci Immunol 2022 Jun 10;7(72):eabl9330. Epub 2022 Jun 10.

University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. Read More

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Extracellular Prostaglandins E1 and E2 and Inflammatory Cytokines Are Regulated by the Senescence Program in Potentially Premalignant Oral Keratinocytes.

Cancers (Basel) 2022 May 26;14(11). Epub 2022 May 26.

Center for Oral Immunobiology and Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK.

Potentially pre-malignant oral lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL, keratinocytes upregulate various extracellular tumor-promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status and was associated with some but not all markers of cellular senescence. Read More

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Inhibition of ATR Reverses a Mitochondrial Respiratory Insufficiency.

Cells 2022 May 24;11(11). Epub 2022 May 24.

The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Diseases that affect the mitochondrial electron transport chain (ETC) often manifest as threshold effect disorders, meaning patients only become symptomatic once a certain level of ETC dysfunction is reached. Cells can invoke mechanisms to circumvent reaching their critical ETC threshold, but it is an ongoing challenge to identify such processes. In the nematode , severe reduction of mitochondrial ETC activity shortens life, but mild reduction actually extends it, providing an opportunity to identify threshold circumvention mechanisms. Read More

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Germline CHEK2 and ATM Variants in Myeloid and Other Hematopoietic Malignancies.

Curr Hematol Malig Rep 2022 Aug 8;17(4):94-104. Epub 2022 Jun 8.

Section of Hematology Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL, 60637, USA.

Purpose Of Review: An intact DNA damage response is crucial to preventing cancer development, including in myeloid and lymphoid malignancies. Deficiencies in the homologous recombination (HR) pathway can lead to defective DNA damage responses, and this can occur through inherited germline mutations in HR pathway genes, such as CHEK2 and ATM. We now understand that germline mutations can be identified frequently (~ 5-10%) in patients with myeloid and lymphoid malignancies, and among the most common of these are CHEK2 and ATM. Read More

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Icaritin inhibits PLK1 to activate DNA damage response in NK/T cell lymphoma and increases sensitivity to GELOX regime.

Mol Ther Oncolytics 2022 Jun 4;25:288-304. Epub 2022 May 4.

Key Laboratory of Medical Molecular Virology of Ministry of Education & Ministry of Health, School of Basic Medical Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive subtype of non-Hodgkin lymphoma. Gemcitabine, oxaliplatin, and L-asparaginase (GELOX) is one of the first-line chemotherapy regimens of NKTCL. Yet, the prognosis of NKTCL is poor. Read More

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In-situ rapid monitoring of nitrate in urban water bodies using Fourier transform infrared attenuated total reflectance spectroscopy (FTIR-ATR) coupled with deconvolution algorithm.

J Environ Manage 2022 Sep 2;317:115452. Epub 2022 Jun 2.

The State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science Chinese Academy of Sciences, Nanjing, 210008, China; College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Urban river and lake systems show important ecological function, and eutrophication frequently occurs and results from human activities due to the limited self-regulating ability. Since nitrate (NO) is one of the key factors causing water eutrophication, its rapid qualification plays critical role in the eutrophication control and management. In this study, water samples were collected from typical water bodies from Nanjing in different seasons, and Fourier transform infrared attenuated total reflectance spectroscopy (FTIR-ATR) was employed for the quantitative determination of NO coupled with algorithms of deconvolution and partial least squares regression (PLSR). Read More

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September 2022

Essential role of CK2α for the interaction and stability of replication fork factors during DNA synthesis and activation of the S-phase checkpoint.

Cell Mol Life Sci 2022 Jun 4;79(6):339. Epub 2022 Jun 4.

Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.

The ataxia telangiectasia mutated and Rad3-related (ATR)-CHK1 pathway is the major signalling cascade activated in response to DNA replication stress. This pathway is associated with the core of the DNA replication machinery comprising CDC45, the replicative MCM2-7 hexamer, GINS (altogether forming the CMG complex), primase-polymerase (POLε, -α, and -δ) complex, and additional fork protection factors such as AND-1, CLASPIN (CLSPN), and TIMELESS/TIPIN. In this study, we report that functional protein kinase CK2α is critical for preserving replisome integrity and for mounting S-phase checkpoint signalling. Read More

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Analysis of ionizing radiation induced DNA damage response in human adult stem cells and differentiated neurons.

Mutat Res Genet Toxicol Environ Mutagen 2022 Jun 18;878:503486. Epub 2022 Apr 18.

Cytogenetic Biodosimetry Laboratory, Radiation Emergency Assistance Center/Training Site, Oak Ridge Institute for Science and Education, Oak Ridge Associated Universities, Oak Ridge, TN, USA. Electronic address:

Findings of neurodegenerative features associated with human radiosensitive syndromes such as Ataxia telangiectasia suggest that DNA repair efficiency is crucial for maintaining the functional integrity of central nervous system. To gain a better understanding of ionizing radiation (IR) induced DNA damage response in undifferentiated and differentiated neural cell types and to evaluate the role of ATM in DNA double strand break (DSB) repair, an in vitro human neural cell differentiation model system was utilized in this study. As compared to adult stem cells, differentiated neurons displayed an attenuated DSB repair response (as judged by the persistence of 53BP1 foci) after IR exposure and the attenuation was even more pronounced in stem cells and neurons after suppression of ATM (Ataxia Telangiectasia Mutated) gene product suggesting the importance of ATM for an optimal DSB repair efficiency in human neural cell types. Read More

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Downregulation of miR-1270 mediates endothelial progenitor cell function in preeclampsia: Role for ATM in the Src/VE-cadherin axis.

FASEB J 2022 07;36(7):e22379

Gynecology Research Unit, Hannover Medical School, Hannover, Germany.

Preeclampsia, a pregnancy-related hypertensive disorder, is associated with endothelial dysfunction and increased cardiovascular risk of the offspring in adulthood. In preeclampsia, endothelial colony-forming cells (ECFC) are reduced in number and function. Recently, we have shown that miR-1270, which is involved in cancer in vitro proliferation, migration, and tumor progression, is downregulated in fetal ECFC from preeclamptic pregnancies. Read More

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Investigation of a Dual siRNA/Chemotherapy Delivery System for Breast Cancer Therapy.

ACS Omega 2022 May 10;7(20):17119-17127. Epub 2022 May 10.

Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre in Biomedical Imaging Technology, The University of Queensland, Brisbane, QLD 4072, Australia.

Multidrug resistance (MDR) is a problem that is often associated with a poor clinical outcome in chemotherapeutic cancer treatment. MDR may potentially be overcome by utilizing synergistic approaches, such as combining siRNA gene therapy and chemotherapy to target different mechanisms of apoptosis. In this study, a strategy is presented for developing multicomponent nanomedicines using orthogonal and compatible chemistries that lead to effective nanotherapeutics. Read More

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A case of wild-type rubella-associated cutaneous granuloma in ataxia telangiectasia.

Pediatr Dermatol 2022 May 29. Epub 2022 May 29.

Department of Immunology, Nottingham University Hospitals NHS Trust, Nottingham, UK.

Granulomatous skin disease is known to be associated with various primary immunodeficiencies, including ataxia telangiectasia (AT). Recent reports of persistence of live vaccine strain rubella within such cutaneous granulomas have raised concern regarding the safety of vaccination. Here we report a case of cutaneous granuloma in association with AT, demonstrating wild type, rather than vaccine strain rubella. Read More

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p53-driven replication stress in nucleoli of malignant epithelial ovarian cancer.

Exp Cell Res 2022 Aug 26;417(2):113225. Epub 2022 May 26.

Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China. Electronic address:

Malignancies including ovarian cancer (OvCa) are genetically unstable. Genomic integrity is maintained by tumor suppressor p53 and DNA damage response network, which crosstalk to each other via not well characterized mechanisms. In this work, we characterize features of damage-related signals in cultured epithelial OvCa cells and tumor biopsies. Read More

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The hallmarks of aging in Ataxia-Telangiectasia.

Ageing Res Rev 2022 May 26;79:101653. Epub 2022 May 26.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Queensland 4072, Australia. Electronic address:

Ataxia-telangiectasia (A-T) is caused by absence of the catalytic activity of ATM, a protein kinase that plays a central role in the DNA damage response, many branches of cellular metabolism, redox and mitochondrial homeostasis, and cell cycle regulation. A-T is a complex disorder characterized mainly by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. It is increasingly recognized that the premature aging component of A-T is an important driver of this disease, and A-T is therefore an attractive model to study the aging process. Read More

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Homozygous ATM mutation due to germline uniparental isodisomy in patient with T acute lymphoblastic leukemia and hepatosplenic T-cell lymphoma.

Cancer Genet 2022 May 21;266-267:15-18. Epub 2022 May 21.

Department of Pediatrics, University of Michigan, Ann Arbor, MI, 48109, United States. Electronic address:

Uniparental disomy has long been recognized as a significant cause of genetic disease in imprinting-associated conditions. More recently, it has increasingly been implicated as a potentially significant cause of autosomal recessive disease. Here we report a case of a patient with a history of leukemia and αβ hepatosplenic T-cell lymphoma who was diagnosed with ataxia telangiectasia via paired tumor-germline testing at age 20. Read More

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Clinicopathological and mutational analysis of esophageal basaloid squamous cell carcinoma.

Virchows Arch 2022 May 31. Epub 2022 May 31.

Department of Human Pathology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Esophageal basaloid squamous cell carcinoma (EBSCC) is a poorly differentiated variant of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinicopathological and molecular biological characteristics of EBSCC and enrolled 58 patients with EBSCCs. Clinicopathological factors including age, sex, tumor size and location, gross tumor type (superficial, protrusive, ulcerative, and unclassifiable), lymphovascular invasion, infiltrative growth, intramural invasion, TNM stage, and dominant histological type were examined. Read More

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