13,862 results match your criteria patient harboring


Differential requirement of NPHP1 for compartmentalized protein localization during photoreceptor outer segment development and maintenance.

PLoS One 2021 7;16(5):e0246358. Epub 2021 May 7.

Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA, United States of America.

Nephrocystin (NPHP1) is a ciliary transition zone protein and its ablation causes nephronophthisis (NPHP) with partially penetrant retinal dystrophy. However, the precise requirements of NPHP1 in photoreceptors are not well understood. Here, we characterize retinal degeneration in a mouse model of NPHP1 and show that NPHP1 is required to prevent infiltration of inner segment plasma membrane proteins into the outer segment during the photoreceptor maturation. Read More

View Article and Full-Text PDF

Chromatin remodeling in replication-uncoupled maintenance DNA methylation and chromosome stability: Insights from ICF syndrome studies.

Authors:
Motoko Unoki

Genes Cells 2021 May 7. Epub 2021 May 7.

Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is characterized by frequent appearance of multiradial chromosomes, which are distinctive chromosome fusions that occur at hypomethylated pericentromeric regions comprising repetitive sequences, in activated lymphocytes. The syndrome is caused by mutations in DNMT3B, ZBTB24, CDCA7, or HELLS. De novo DNA methylation is likely defective in patients with ICF syndrome harboring mutations in DNMT3B, whereas accumulating evidence suggests that replication-uncoupled maintenance DNA methylation of late-replicating regions is impaired in patients with ICF syndrome harboring mutations in ZBTB24, CDCA7, or HELLS. Read More

View Article and Full-Text PDF

Alectinib for Miliary Lung Metastasis in -Positive Lung Adenocarcinoma.

Onco Targets Ther 2021 30;14:2911-2915. Epub 2021 Apr 30.

Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background: Miliary pulmonary metastasis characterized by tiny nodules is a rare metastatic pattern in advanced non-small cell lung cancer (NSCLC) and is usually seen in patients harboring an mutation, and amylase-producing lung cancer is highly uncommon and rarely reported in NSCLC patients who have an mutation.

Case: A 32-year-old Japanese female was found to have miliary pulmonary nodules throughout both lung fields on a chest x-ray examination during an annual health check-up. Further examination by computed tomography (CT) revealed diffuse, bilateral, miliary nodules. Read More

View Article and Full-Text PDF

First report of a bla metallo-β-lactamase-possessing Klebsiella michiganensis.

J Glob Antimicrob Resist 2021 May 3. Epub 2021 May 3.

Institute for Infectious Diseases (IFIK), University of Bern. Electronic address:

Background: Klebsiella michiganensis is an emerging pathogen. As for Klebsiella pneumoniae, this species is able to acquire antibiotic resistance genes (ARGs) via mobile genetic elements. In this context, K. Read More

View Article and Full-Text PDF

Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study.

Ther Adv Neurol Disord 2021 9;14:1756286420987939. Epub 2021 Apr 9.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.

Background And Aims: The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA <7 mm.

Methods: This prospective, multicenter cohort study consecutively enrolled patients with concurrent UIA <7 mm and ischemic cerebrovascular disease from four hospitals between 2016 and 2019. Read More

View Article and Full-Text PDF

Estrogen Receptor β Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer.

Anticancer Res 2021 May;41(5):2371-2381

Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan;

Background/aim: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has posed serious clinical problems in the treatment of lung adenocarcinoma (LADC) patients harboring relevant EGFR mutations. In this study, we explored the role of estrogen receptor β (ERβ) in the development of acquired resistance to EGFR-TKIs in human LADC.

Materials And Methods: First, the role of ERβ in erlotinib resistance of LADC cell lines (PC9/ER) was examined. Read More

View Article and Full-Text PDF

CEBPA bZip Mutations are Associated with Favorable Prognosis in de novo AML: A Report from the Children's Oncology Group.

Blood 2021 May 5. Epub 2021 May 5.

Fred Hutchinson Cancer Research Center, seattle, Washington, United States.

Bi-allelic CEBPA mutations are associated with favorable outcomes in AML. We evaluated the clinical and biologic implications of CEBPA-bZip mutations in childhood/young adult newly diagnosed AML. CEBPA-bZip mutation status was determined in 2,958 AML patients enrolled on COG trials (NCT00003790, NCT0007174, NCT00372593, NCT01379181). Read More

View Article and Full-Text PDF

Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Adjuvant Setting for Patients with Resected Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer: A Meta-Analysis with 11 Trials.

Oncol Res Treat 2021 May 5:1-9. Epub 2021 May 5.

Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, China.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have recently become the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. This study aimed to define the role of EGFR-TKI treatment in the adjuvant setting of patients with resected EGFR-mutant NSCLC.

Methods: Three online databases (PubMed, Embase, and the Cochrane Library) were used to conduct systematic research to search for studies published before June 1, 2020. Read More

View Article and Full-Text PDF

Phase I-II open label multicenter study of palbociclib + vemurafenib in BRAFV600MUT metastatic melanoma patients: uncovering CHEK2 as a major response mechanism.

Clin Cancer Res 2021 May 4. Epub 2021 May 4.

Dermatology Department, AP-HP, Hopital St Louis

Purpose: In BRAFV600MUT metastatic melanoma, cyclin-D-CDK4/6-INK4-Rb pathway alterations are involved in resistance to MAPK inhibitors, suggesting a clinical benefit of CDK4 inhibitors. In this phase I-II study, we aimed to establish the maximum tolerated dose (MTD) of palbociclib when added to vemurafenib.

Patients And Methods: BRAFV600E/KMUT metastatic melanoma patients harboring CDKN2A loss and RB1 expression were included and stratified into 2 groups according to previous BRAF inhibitor treatment (no:strata 1; yes:strata 2). Read More

View Article and Full-Text PDF

Transient Response of Olaparib on Pulmonary Artery Sarcoma Harboring Multiple Homologous Recombinant Repair Gene Alterations.

J Pers Med 2021 Apr 29;11(5). Epub 2021 Apr 29.

ACT Genomics Co., Ltd., Taipei 114, Taiwan.

Primary pulmonary artery sarcoma (PPAS) is a rare malignancy arising from mesenchymal pulmonary artery cells and mimics pulmonary embolism. Palliative chemotherapy such as anthracycline- or ifosfamide-based regimens and targeted therapy are the only options. However, the evidence of clinically beneficial systemic treatment is scarce. Read More

View Article and Full-Text PDF

Genomic Characterization of Concurrent Alterations in Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Mutations.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

An increasing number of driver genomic alterations with potential targeted treatments have been identified in non-small cell lung cancer (NSCLC). Much less is known about the incidence and different distribution of concurrent alterations, as identified by comprehensive genomic profiling in oncogene-addicted NSCLCs. Genomic data from advanced NSCLC consecutively analyzed using a broad next-generation sequencing panel were retrospectively collected. Read More

View Article and Full-Text PDF

The Role of Left-Atrial Mechanics Assessed by Two-Dimensional Speckle-Tracking Echocardiography to Differentiate Hypertrophic Cardiomyopathy from Hypertensive Left-Ventricular Hypertrophy.

Diagnostics (Basel) 2021 Apr 30;11(5). Epub 2021 Apr 30.

Cardio-thoracic Department, University of Medicine and Pharmacy Carol Davila, Eroii Sanitari Bvd. 8, 050474 Bucharest, Romania.

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown.

Methods: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. Read More

View Article and Full-Text PDF

Crizotinib resistance conferred by BRAF V600E mutation in non-small cell lung cancer harboring an oncogenic ROS1 fusion.

Cancer Treat Res Commun 2021 Apr 20;27:100377. Epub 2021 Apr 20.

Department of General Internal Medicine, Guangxi Medical University Affiliated Cancer Hospital, No. 71 Hedi Road, Nanning, Guangxi, China. Electronic address:

Non-small cell lung cancer (NSCLC) patients with oncogenic ROS1 rearrangements would inevitably develop drug resistance and disease progression after receiving targeted oncogene therapy. Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation. Read More

View Article and Full-Text PDF

Multidrug-resistant Klebsiella pneumoniae harboring extended spectrum β-lactamase encoding genes isolated from human septicemias.

PLoS One 2021 4;16(5):e0250525. Epub 2021 May 4.

Department of Veterinary Sciences, Microbiology and Antibiotic Resistance Team (MicroART), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.

Klebsiella pneumoniae is a major pathogen implicated in nosocomial infections. Extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates are a public health concern. Read More

View Article and Full-Text PDF

Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy.

Hum Genet 2021 May 4. Epub 2021 May 4.

CHU Sainte-Justine Research Center, Montreal, QC, H3T 1C5, Canada.

Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while CHD5-related disorders are still unknown. Thanks to GeneMatcher and international collaborations, we assembled a cohort of 16 unrelated individuals harboring heterozygous CHD5 variants, all identified by exome sequencing. Read More

View Article and Full-Text PDF

Limited effect of afatinib in a non-small cell lung cancer patient harboring an epidermal growth factor receptor K860I missense mutation: A case report.

Thorac Cancer 2021 May 4. Epub 2021 May 4.

Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are key drugs in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, first-generation EGFR-TKIs, such as gefitinib and erlotinib, are not effective in patients with uncommon EGFR mutations. In contrast, efficacy of afatinib has been reported in some types of uncommon EGFR mutation such as G710X, L861Q. The effect of afatinib in NSCLC patients with the EGFR K860I mutation has been shown in vitro, but its clinical efficacy has not been demonstrated. Read More

View Article and Full-Text PDF

Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype.

Genet Med 2021 May 3. Epub 2021 May 3.

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Purpose: Despite a few recent reports of patients harboring truncating variants in NSD2, a gene considered critical for the Wolf-Hirschhorn syndrome (WHS) phenotype, the clinical spectrum associated with NSD2 pathogenic variants remains poorly understood.

Methods: We collected a comprehensive series of 18 unpublished patients carrying heterozygous missense, elongating, or truncating NSD2 variants; compared their clinical data to the typical WHS phenotype after pooling them with ten previously described patients; and assessed the underlying molecular mechanism by structural modeling and measuring methylation activity in vitro.

Results: The core NSD2-associated phenotype includes mostly mild developmental delay, prenatal-onset growth retardation, low body mass index, and characteristic facial features distinct from WHS. Read More

View Article and Full-Text PDF

Development of BRAF V600E Mutation in NRAS Q61L Mutated Rectal Cancer.

Ann Clin Lab Sci 2021 Mar;51(2):262-266

Laboratory of Molecular Medicine, Ordos Central Hospital, Ordos

BRAF and NRAS are oncogenes in the RAS/RAF/MEK/MAP-kinase signaling pathway. Coexistent mutations of BRAF and NRAS in a single colorectal cancer patient have always been considered mutually exclusive or at least rare. The clinical outcome of these patients remains undetermined. Read More

View Article and Full-Text PDF

Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment.

World J Surg Oncol 2021 Apr 30;19(1):136. Epub 2021 Apr 30.

Department of Pathology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.

Background: Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Read More

View Article and Full-Text PDF

Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations.

BMC Cancer 2021 May 3;21(1):495. Epub 2021 May 3.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib.

Methods: We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. Read More

View Article and Full-Text PDF

Lung carcinoid tumors with Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) exhibit pejorative pathological features.

Lung Cancer 2021 Apr 30;156:117-121. Epub 2021 Apr 30.

Department of Thoracic Surgery, Hôpital Cochin, APHP.CUP, Université de Paris, France. Electronic address:

Introduction: Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors.

Material And Methods: We reviewed all patients operated on for curative-intent resection of carcinoid tumor in our department from 2001 to 2020. Read More

View Article and Full-Text PDF

Decreased temperature increases the expression of a disordered bacterial late embryogenesis abundant (LEA) protein that enhances natural transformation.

Virulence 2021 Dec;12(1):1239-1257

Department of Life Technologies, University of Turku, Turku, Finland.

Late embryogenesis abundant (LEA) proteins are important players in the management of responses to stressful conditions, such as drought, high salinity, and changes in temperature. Many LEA proteins do not have defined three-dimensional structures, so they are intrinsically disordered proteins (IDPs) and are often highly hydrophilic. Although LEA-like sequences have been identified in bacterial genomes, the functions of bacterial LEA proteins have been studied only recently. Read More

View Article and Full-Text PDF
December 2021

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

Invest Ophthalmol Vis Sci 2021 May;62(6)

Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.

Purpose: The purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.

Methods: Patients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Read More

View Article and Full-Text PDF

Dravet syndrome and Dravet syndrome-like phenotype: a systematic review of the SCN1A and PCDH19 variants.

Neurogenetics 2021 May 3. Epub 2021 May 3.

Laboratory of Cellular and Molecular Biology of Tumors and Bioactive Compounds and Laboratory of Human and Medical Genetics, São Francisco University, Bragança Paulista, São Paulo, Brazil.

Dravet syndrome (DS) is a rare and severe epileptic syndrome of childhood with prevalence between 1/22,000 and 1/49,900 of live births. Approximately 80% of patients with this syndrome present SCN1A pathogenic variants, which encodes an alpha subunit of a neural voltage-dependent sodium channel. There is a correlation between PCDH19 pathogenic variants, encodes the protocadherin 19, and a similar disease to DS known as DS-like phenotype. Read More

View Article and Full-Text PDF

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment.

Front Oncol 2021 15;11:649843. Epub 2021 Apr 15.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The acquired C797X mutation has been identified as the most notable resistance to osimertinib, and novel secondary mutations of L718 and L792 residues have also been demonstrated to confer osimertinib resistance, making the choice of medication after osimertinib treatment a quandary. Dacomitinib has been reported to have potential impact on patients acquiring rare compound mutations after osimertinib resistance; however, little evidence is available to date. In five lung adenocarcinoma patients resistant to later-line osimertinib, recurrent mutations at L792 and/or L718 were identified using targeted next-generation sequencing of tissue or cell-free DNA from plasma or pleural effusion. Read More

View Article and Full-Text PDF

Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an gene fusion.

Authors:
Fabián Pitoia

Clin Case Rep 2021 Apr 20;9(4):1905-1912. Epub 2021 Feb 20.

Division of Endocrinology, Hospital de Clínicas University of Buenos Aires Buenos Aires Argentina.

Larotrectinib, a highly selective TRK inhibitor, was administered to a patient with rapidly progressing radioactive iodine-refractory papillary NTRK3 fusion-positive thyroid cancer. The patient achieved a durable (sustained for 11 months) complete response after 2 months of treatment and complete intracranial responses in metastatic brain lesions after 7 months of treatment. Larotrectinib may provide a therapeutic route for patients with RAI-R-differentiated thyroid cancer who might otherwise have few treatment options. Read More

View Article and Full-Text PDF

Case Report: Expanding Clinical, Immunological and Genetic Findings in Sideroblastic Anemia With Immunodeficiency, Fevers and Development Delay (SIFD) Syndrome.

Front Immunol 2021 14;12:586320. Epub 2021 Apr 14.

Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil.

Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. Read More

View Article and Full-Text PDF

Periodontal microorganisms and diagnosis of malignancy: A cross-sectional study.

Tumour Biol 2021 ;43(1):1-9

Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Oral infections associate statistically with cancer.

Objective: We hypothesized that certain periodontal microorganisms might specifically link to malignancies in general and set out to investigate this in our ongoing cohort study.

Methods: A sample of 99 clinically examined patients from our cohort of 1676 subjects was used to statistically investigate the associations between harboring periodontal microorganisms Aggregatibacter actinomycetemcomitans (A. Read More

View Article and Full-Text PDF
January 2021

Prevalence and antibiotic susceptibility trends of periodontal pathogens in the subgingival microbiota of German periodontitis patients: A retrospective surveillance study.

J Clin Periodontol 2021 May 2. Epub 2021 May 2.

Division of Microbiology, Paul-Ehrlich-Institut, Paul-Ehrlichstr. 51-59, D-63225, Langen, Germany.

Objective: This retrospective surveillance study aimed to follow periodontitis-associated bacterial profiles and to identify time-dependent changes in antibiotic susceptibility patterns.

Materials And Methods: From 2008 to 2015 bacterial specimen from deep periodontal pockets were collected from a total of 7804 German adults diagnosed with periodontitis. Presence of selected bacteria was confirmed by anaerobic culture and nucleic acid amplification. Read More

View Article and Full-Text PDF