Purpose: Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene on chromosome 15q14. Co-occurring alternations have not been fully characterized.
Methods: We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).
Gliomas are highly malignant brain tumours that remain refractory to treatment. Treatment is typically surgical intervention followed by concomitant temozolomide and radiotherapy; however patient prognosis remains poor. Voltage gated ion channels have emerged as novel targets in cancer therapy and inhibition of a potassium selective subtype (hERG, Kv11.
View Article and Find Full Text PDFWe report a woman in her 30s with dysferlinopathy whose diagnosis was masked by superimposed hypothyroidism. Laboratory studies revealed Hashimoto's thyroiditis and markedly raised serum creatine kinase (CK of 6255 U/L; reference range 0-170 U/L). Electromyography, nerve conduction studies and MRI of the hip and thigh were consistent with a diagnosis of hypothyroid myopathy, but thyroxine failed to resolve her clinical presentation or normalise the CK level.
View Article and Find Full Text PDFNUT carcinoma is a rare subcategory of squamous cell carcinoma. The latter is primarily characterized by the fusion of the coding sequence on chromosome 15q14 with BRD4 or BRD3, both of which are acetyl-histone binding bromodomains. This tumor is often misdiagnosed due to its rarity and its histological similarity with other squamous cell carcinomas.
View Article and Find Full Text PDFWe present the first known case of a patient with -driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a fusion led to the diagnosis of NUT carcinoma.
View Article and Find Full Text PDFIntroduction: NUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports.
View Article and Find Full Text PDFUnlabelled: NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC.
View Article and Find Full Text PDFNight-time is a period of great significance for many people who report paranormal experiences. However, there is limited understanding of the associations between sleep variables and seemingly paranormal experiences and/or beliefs. The aim of this review is to improve our understanding of these associations while unifying a currently fragmented literature-base into a structured, practical review.
View Article and Find Full Text PDFStudy Objectives: Isolated sleep paralysis is a benign but frightening condition characterised by a temporary inability to move at sleep onset or upon awakening. Despite the prevalence of this condition, little is known concerning its clinical features, associated demographic characteristics, and prevention as well as disruption strategies.
Methods: An online cross-sectional study was conducted.
Previous studies have found significant associations between paranormal beliefs and sleep variables. However, these have been conducted on a small scale and are limited in the number of sleep variables investigated. This study aims to fill a gap in the literature by investigating paranormal beliefs in relation to a wide range of sleep variables in a large sample.
View Article and Find Full Text PDFWe recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.
View Article and Find Full Text PDFNUT carcinoma (NC) is a rare subtype of squamous cell carcinoma defined by NUTM1 rearrangements encoding NUT fusion oncoproteins (the most frequent fusion partner being BRD4 ) that carries a very poor prognosis, with most patients dying in under 1 year. Only rare primary thyroid NCs have been reported. Here, we evaluated a series of 14 cases.
View Article and Find Full Text PDFNUT carcinoma (NC) is an extremely aggressive tumor and current treatment regimens offer patients a median survival of six months only. This article reports on the first in vitro studies using immunovirotherapy as a promising therapy option for NC and its feasible combination with BET inhibitors (iBET). Using NC cell lines harboring the BRD4-NUT fusion protein, the cytotoxicity of oncolytic virus (T-VEC) and the iBET compounds BI894999 and GSK525762 were assessed in vitro in monotherapeutic and combinatorial approaches.
View Article and Find Full Text PDFHum Pathol
August 2022
NUT carcinoma (NC) is a rare malignancy with aggressive clinical behavior, defined by rearrangements involving the NUTM1 gene locus. This entity is often under-recognized and its diagnosis may be challenging. In this study, we describe a subset of patients that, despite the molecularly proven diagnosis of NC, show improved outcomes.
View Article and Find Full Text PDFNUT carcinoma is a rare, aggressive cancer defined by rearrangements of the NUTM1 gene. No routinely effective treatments of NUT carcinoma exist, despite harboring a targetable oncoprotein, most commonly BRD4-NUT. The vast majority of cases are fatal.
View Article and Find Full Text PDFIn type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Although tracrRNAs are diverse in sequence and structure across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for Cas9 is not fully understood. Here, we reveal the programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9, and in doing so, redefine the capabilities of Cas9 proteins and the sources of crRNAs, providing new biosensing applications for type II CRISPR systems.
View Article and Find Full Text PDFBackground And Objectives: Epilepsy is associated with an increased risk of cardiovascular disease and premature mortality, including sudden unexpected death in epilepsy (SUDEP). Serious cardiac arrythmias might go undetected in routine epilepsy and cardiac investigations.
Methods: This prospective cohort study aimed to detect cardiac arrhythmias in patients with chronic drug-resistant epilepsy (≥5 years duration) using subcutaneous cardiac monitors for a minimum follow-up duration of 12 months.
Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive, undifferentiated carcinoma that harbors a characteristic rearrangement of the NUTM1 gene. The majority arise in adolescents and young adults especially from the midline structures of the thorax, head, and neck. Until the present, there have only been three reported cases of NUT carcinoma of the submandibular gland, two of which were reported in children and another one in an adult from Korea.
View Article and Find Full Text PDFInt J Cancer
March 2022