43,099 results match your criteria cancer evolution

Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants in S. cerevisiae.

Genetics 2021 Apr 12. Epub 2021 Apr 12.

Genome Sciences Department, University of Washington, Seattle, WA 98195, USA.

Despite the fundamental importance of mutation rate as a driving force in evolution and disease risk, common methods to assay mutation rate are time consuming and tedious. Established methods such as fluctuation tests and mutation accumulation experiments are low-throughput and often require significant optimization to ensure accuracy. We established a new method to determine the mutation rate of many strains simultaneously by tracking mutation events in a chemostat continuous culture device and applying deep sequencing to link mutations to alleles of a DNA-repair gene. Read More

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Technique of open and minimally invasive intrathoracic reconstruction following esophagectomy-an expert consensus based on a modified Delphi process.

Dis Esophagus 2021 Jan 16. Epub 2021 Jan 16.

Department of General, Visceral and Cancer Surgery, University Hospital Cologne, Cologne, Germany.

Background: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology. Read More

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January 2021

Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues.

Science 2021 Apr 12. Epub 2021 Apr 12.

Department of Pathology, Stanford University, Stanford, CA 94305, USA.

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Read More

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Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability-High Gastric Cancer.

Cancer Discov 2021 Apr 12. Epub 2021 Apr 12.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Samsung Medical Center, Sungkyunkwan University School of Medicine

Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers (GC) and associated with clinical response to anti-programmed death (PD)-1 antibodies. However, 50% of microsatellite instability-high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in advanced MSI-H GC patients and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. Read More

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High-throughput label-free detection of DNA-to-RNA transcription inhibition using brightfield microscopy and deep neural networks.

Comput Biol Med 2021 Apr 4;133:104371. Epub 2021 Apr 4.

Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Center, Villejuif, France; Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China; Po^le de Biologie, Ho^pital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Drug discovery is in constant evolution and major advances have led to the development of in vitro high-throughput technologies, facilitating the rapid assessment of cellular phenotypes. One such phenotype is immunogenic cell death, which occurs partly as a consequence of inhibited RNA synthesis. Automated cell-imaging offers the possibility of combining high-throughput with high-content data acquisition through the simultaneous computation of a multitude of cellular features. Read More

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Beyond cancer cells: Targeting the tumour microenvironment with gene therapy and armed oncolytic virus.

Mol Ther 2021 Apr 9. Epub 2021 Apr 9.

Department Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address:

Cancer gene therapies are usually designed either to express wild type copies of tumour suppressor genes or to exploit tumour-associated phenotypic changes to endow selective cytotoxicity. However, these approaches become less relevant to cancers that contain many independent mutations and the situation is made more complex by our increased understanding of clonal evolution of tumours, meaning that different metastases and even regions of the same tumour mass have distinct mutational and phenotypic profiles. In contrast, the relatively genetically stable tumour microenvironment (TME) therefore provides an appealing therapeutic target, particular since it plays an essential role in promoting cancer growth, immune tolerance and acquired resistance to many therapies. Read More

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Do we really understand how drug eluted from stents modulates arterial healing?

Int J Pharm 2021 Apr 9:120575. Epub 2021 Apr 9.

Division of Biomedical Engineering, University of Glasgow, Glasgow, UK. Electronic address:

The advent of drug-eluting stents (DES) has revolutionised the treatment of coronary artery disease. These devices, coated with anti-proliferative drugs, are deployed into stenosed or occluded vessels, compressing the plaque to restore natural blood flow, whilst simultaneously combating the evolution of restenotic tissue. Since the development of the first stent, extensive research has investigated how further advancements in stent technology can improve patient outcome. Read More

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Directed Evolution of Stabilized Monomeric CD19 for Monovalent CAR Interaction Studies and Monitoring of CAR-T Cell Patients.

ACS Synth Biol 2021 Apr 12. Epub 2021 Apr 12.

Department of Chemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.

CD19 is among the most relevant targets in cancer immunotherapy. However, its extracellular domain (ECD) is prone to aggregation and misfolding, representing a major obstacle for the development and analysis of CD19-targeted therapeutics. Here, we engineered stabilized CD19-ECD (termed SuperFolder) variants, which also showed improved expression rates and, in contrast to the wild type protein, they could be efficiently purified in their monomeric forms. Read More

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Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016.

Cell Rep Med 2021 Apr 5:100255. Epub 2021 Apr 5.

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Read More

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Benzothiazole Amides as TRPC3/6 Inhibitors for Gastric Cancer Treatment.

ACS Omega 2021 Apr 24;6(13):9196-9203. Epub 2021 Mar 24.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education; Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.

Transient receptor potential canonical channel 6 (TRPC6) has been implicated in many kinds of malignant tumors, but very few potent TRPC6 antagonists are available. In this study, a benzothiazole amide derivative was discovered as a TRPC6 activator in a cell-based high-throughput screening. A series of benzothiazole amide derivatives were designed and synthesized. Read More

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Case Report: Cutaneous Squamous Cell Carcinoma Arising From the Ulcer of the Lesions of Dupuytren's Disease on the Palm.

Front Oncol 2021 25;11:638395. Epub 2021 Mar 25.

Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Dupuytren's disease is a benign fibromatosis that mainly involves the fascia of the palm and digits. The relationship between Dupuytren's disease and the evolution of cutaneous squamous cell carcinoma is still unclear. Here we report the case of a 52-year-old female with squamous cell carcinoma arising from the ulcer of the lesions of Dupuytren's disease on the left palm. Read More

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Expression and clinical implications of estrogen receptors in thoracic malignancies: a narrative review.

J Thorac Dis 2021 Mar;13(3):1851-1863

Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy.

Thoracic malignancies represent a significant global health burden with incidence and mortality increasing year by year. Thoracic cancer prognosis and treatment options depend on several factors, including the type and size of the tumor, its location, and the overall health status of patients. Gender represents an important prognostic variable in thoracic malignancies. Read More

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An Overview of Pretreatment and Analysis of Nucleotides in Different Samples (Update since 2010).

Crit Rev Anal Chem 2021 Apr 12:1-20. Epub 2021 Apr 12.

School of Pharmacy, China Medical University, Shenyang, China.

Nucleotides, which are important low-molecular-weight compounds present in organisms, are precursors of nucleic acids and participate in various regulatory and metabolic functions. Sensitive and valid methods for monitoring and determining nucleotides and nucleosides in different samples are urgently required. Due to the presence of numerous endogenous interferences in complex matrices and the high polarity of the molecules of the phosphate moiety, the determination of nucleotide content is challenging. Read More

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Transoral endoscopic vestibular approach for thyroidectomy and parathyroidectomy - From promise to practice.

Am J Otolaryngol 2021 Mar 31;42(5):103022. Epub 2021 Mar 31.

A.R.M. Center of Otolaryngology Head and Neck Surgery, Assuta Medical Center, Tel Aviv, Israel.

Objectives: To describe the evolution and recent series on transoral endoscopic vestibular approach thyroidectomy and parathyroidectomy (TOET/PVA).

Data Sources: PubMed, Google Scholar.

Review Methods: Review of the available English literature. Read More

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Retrieving the deleterious mutations before extinction: genome-wide comparison of shared derived mutations in liver cancer and normal population.

Postgrad Med J 2021 Apr 9. Epub 2021 Apr 9.

Department of Interventional Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China

Study Purpose: Deleterious mutations would be rapidly purged from natural populations along with the extinction of their carriers. The currently observed mutations in existing species are mostly neutral. The inaccessibility of deleterious mutations impedes the functional studies on how these mutations affect the fitness at individual level. Read More

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Werner helicase is a synthetic-lethal vulnerability in Mismatch Repair-Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy and Immunotherapy.

Cancer Discov 2021 Apr 9. Epub 2021 Apr 9.

Cancer Programme, Wellcome Sanger Institute

Targeted therapies, chemotherapy, and immunotherapy are used to treat patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC). The clinical effectiveness of targeted therapy and chemotherapy is limited by resistance and drug toxicities, and about half of immunotherapy patients are refractory to immune checkpoint inhibitors. Loss of Werner syndrome ATP-dependent helicase (WRN) is a synthetic-lethality in dMMR/MSI-H cells. Read More

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Avidity optimization of a MAGE-A1 specific TCR with somatic hypermutation.

Eur J Immunol 2021 Apr 9. Epub 2021 Apr 9.

Department of immunology, Weizmann Institute of Science, Rehovot, 76100, Israel.

A T cell receptor (TCR) with optimal avidity to a tumor antigen can be used to redirect T cells to eradicate cancer cells via adoptive cell transfer (ACT). Cancer testis antigens (CTAs) are attractive targets because they are expressed in the testis, which is immune-privileged, and in the tumor. However, CTAs are self-antigens and natural TCRs to CTAs have low affinity/avidity due to central tolerance. Read More

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Horizons in Veterinary Precision Oncology: Fundamentals of Cancer Genomics and Applications of Liquid Biopsy for the Detection, Characterization, and Management of Cancer in Dogs.

Front Vet Sci 2021 23;8:664718. Epub 2021 Mar 23.

PetDx, La Jolla, CA, United States.

Cancer is the leading cause of death in dogs, in part because many cases are identified at an advanced stage when clinical signs have developed, and prognosis is poor. Increased understanding of cancer as a disease of the genome has led to the introduction of liquid biopsy testing, allowing for detection of genomic alterations in cell-free DNA fragments in blood to facilitate earlier detection, characterization, and management of cancer through non-invasive means. Recent discoveries in the areas of genomics and oncology have provided a deeper understanding of the molecular origins and evolution of cancer, and of the "one health" similarities between humans and dogs that underlie the field of comparative oncology. Read More

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Immunosuppressive Microenvironment Revealed by Immune Cell Landscape in Pre-metastatic Liver of Colorectal Cancer.

Front Oncol 2021 23;11:620688. Epub 2021 Mar 23.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Colorectal cancer, the fourth leading cause of cancer mortality, is prone to metastasis, especially to the liver. The pre-metastatic microenvironment comprising various resident stromal cells and immune cells is essential for metastasis. However, how the dynamic evolution of immune components facilitates pre-metastatic niche formation remains unclear. Read More

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Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia.

Nat Genet 2021 Apr 8. Epub 2021 Apr 8.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Transposable elements or transposons are major players in genetic variability and genome evolution. Aberrant activation of long interspersed element-1 (LINE-1 or L1) retrotransposons is common in human cancers, yet their tumor-type-specific functions are poorly characterized. We identified MPHOSPH8/MPP8, a component of the human silencing hub (HUSH) complex, as an acute myeloid leukemia (AML)-selective dependency by epigenetic regulator-focused CRISPR screening. Read More

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Can we prevent childhood Leukaemia?

Leukemia 2021 Apr 9. Epub 2021 Apr 9.

Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.

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Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival.

Pancreatology 2021 Apr 1. Epub 2021 Apr 1.

Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: CD73, a newly recognized immune checkpoint mediator, is expressed in several types of malignancies. However, CD73 expression and its impact on tumor microenvironment and clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) remain unclear.

Methods: This study included two cohorts: 138 patients from our institution (MDA) and 176 patients from TCGA dataset. Read More

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A human coronavirus evolves antigenically to escape antibody immunity.

PLoS Pathog 2021 04 8;17(4):e1009453. Epub 2021 Apr 8.

Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. Read More

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Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates.

Front Med (Lausanne) 2021 22;8:645543. Epub 2021 Mar 22.

Statistical Service, Istituto Superiore di Sanità, Rome, Italy.

In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death. Read More

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The structure, function and evolution of a complete human chromosome 8.

Nature 2021 Apr 7. Epub 2021 Apr 7.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

The complete assembly of each human chromosome is essential for understanding human biology and evolution. Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2. Read More

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Structural variant evolution after telomere crisis.

Nat Commun 2021 04 7;12(1):2093. Epub 2021 Apr 7.

Department of Pathology and Laboratory Medicine, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Telomere crisis contributes to cancer genome evolution, yet only a subset of cancers display breakage-fusion-bridge (BFB) cycles and chromothripsis, hallmarks of experimental telomere crisis identified in previous studies. We examine the spectrum of structural variants (SVs) instigated by natural telomere crisis. Eight spontaneous post-crisis clones did not show prominent patterns of BFB cycles or chromothripsis. Read More

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Response to correspondence on "Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation".

Channabasavaiah B Gurumurthy Aidan R O'Brien Rolen M Quadros John Adams Pilar Alcaide Shinya Ayabe Johnathan Ballard Surinder K Batra Marie-Claude Beauchamp Kathleen A Becker Guillaume Bernas David Brough Francisco Carrillo-Salinas Wesley Chan Hanying Chen Ruby Dawson Victoria DeMambro Jinke D'Hont Katharine Dibb James D Eudy Lin Gan Jing Gao Amy Gonzales Anyonya Guntur Huiping Guo Donald W Harms Anne Harrington Kathryn E Hentges Neil Humphreys Shiho Imai Hideshi Ishii Mizuho Iwama Eric Jonasch Michelle Karolak Bernard Keavney Nay-Chi Khin Masamitsu Konno Yuko Kotani Yayoi Kunihiro Imayavaramban Lakshmanan Catherine Larochelle Catherine B Lawrence Lin Li Volkhard Lindner Xian-De Liu Gloria Lopez-Castejon Andrew Loudon Jenna Lowe Loydie Jerome-Majeweska Taiji Matsusaka Hiromi Miura Yoshiki Miyasaka Benjamin Morpurgo Katherine Motyl Yo-Ichi Nabeshima Koji Nakade Toshiaki Nakashiba Kenichi Nakashima Yuichi Obata Sanae Ogiwara Mariette Ouellet Leif Oxburgh Sandra Piltz Ilka Pinz Moorthy P Ponnusamy David Ray Ronald J Redder Clifford J Rosen Nikki Ross Mark T Ruhe Larisa Ryzhova Ane M Salvador Sabrina Shameen Alam Radislav Sedlacek Karan Sharma Chad Smith Katrien Staes Lora Starrs Fumihiro Sugiyama Satoru Takahashi Tomohiro Tanaka Andrew Trafford Yoshihiro Uno Leen Vanhoutte Frederique Vanrockeghem Brandon J Willis Christian S Wright Yuko Yamauchi Xin Yi Kazuto Yoshimi Xuesong Zhang Yu Zhang Masato Ohtsuka Satyabrata Das Daniel J Garry Tino Hochepied Paul Thomas Jan Parker-Thornburg Antony D Adamson Atsushi Yoshiki Jean-Francois Schmouth Andrei Golovko William R Thompson K C Kent Lloyd Joshua A Wood Mitra Cowan Tomoji Mashimo Seiya Mizuno Hao Zhu Petr Kasparek Lucy Liaw Joseph M Miano Gaetan Burgio

Genome Biol 2021 Apr 7;22(1):99. Epub 2021 Apr 7.

Department of Immunology and Infectious Disease, the John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

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Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma.

BMC Cancer 2021 Apr 8;21(1):376. Epub 2021 Apr 8.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background And Aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. Read More

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