CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

Background: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population.

Methods: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020).

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

Purpose: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET).

Circulating Tumour DNA in Melanoma-Clinic Ready?

Purpose Of Review: Liquid biopsies, including circulating tumour DNA (ctDNA), can inform a variety of clinical questions. This review examines the potential role of ctDNA as a clinical tool to inform clinical decision-making from early to late stage cutaneous melanoma.

Recent Findings: In pre-clinical studies, ctDNA has been shown to detect minimal residual disease and molecular relapse; predict and monitor response to therapy; and identify key resistance mechanisms.

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study.

Background: Breast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years.

Methods: 14 cancer centres participated in this national UK retrospective study.

Effect of β /β -adrenoceptor blockade on β -adrenoceptor activity in the rat cremaster muscle artery.

Background And Purpose: The physiological role of vascular β -adrenoceptors is not fully understood. Recent evidence suggests cardiac β -adrenoceptors are functionally effective after down-regulation of β /β -adrenoceptors. The functional interaction between the β -adrenoceptor and other β-adrenoceptor subtypes in rat striated muscle arteries was investigated.

TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats.

This study investigated the expression and function of transient receptor potential vanilloid type-3 ion channels (TRPV3) in uterine radial arteries isolated from non-pregnant and twenty-day pregnant rats. Immunohistochemistry (IHC) suggested TRPV3 is primarily localized to the smooth muscle in arteries from both non-pregnant and pregnant rats. IHC using C' targeted antibody, and qPCR of TRPV3 mRNA, suggested pregnancy increased arterial TRPV3 expression.

Molecular and functional significance of Ca(2+)-activated Cl(-) channels in pulmonary arterial smooth muscle.

Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca(2+) levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K(+) channels (e.

Anoctamins and gastrointestinal smooth muscle excitability.

Interstitial cells of Cajal (ICC) generate electrical pacemaker activity in gastrointestinal smooth muscles. We investigated whether Tmem16a, which encodes anoctamin 1 (ANO1), a Ca(2+)-activated Cl(-) channel, might be involved in pacemaker activity in ICC. The Tmem16a transcripts and ANO1 were expressed robustly in GI muscles, specifically in ICC in murine, non-human primate (Macaca fascicularis) and human GI tracts.

Electrical slow waves in the mouse oviduct are dependent upon a calcium activated chloride conductance encoded by Tmem16a.

Myosalpinx contractions are critical for oocyte transport along the oviduct. A specialized population of pacemaker cells-oviduct interstitial cells of Cajal-generate slow waves, the electrical events underlying myosalpinx contractions. The ionic basis of oviduct pacemaker activity is unknown.

Electrical slow waves in the mouse oviduct are dependent on extracellular and intracellular calcium sources.

Spontaneous contractions of the myosalpinx are critical for oocyte transport along the oviduct. Slow waves, the electrical events that underlie myosalpinx contractions, are generated by a specialized network of pacemaker cells called oviduct interstitial cells of Cajal (ICC-OVI). The ionic basis of oviduct pacemaker activity is unknown.

Increased complexity of Tmem16a/Anoctamin 1 transcript alternative splicing.

Background: TMEM16A (Anoctamin 1; ANO1) is an eight transmembrane protein that functions as a calcium-activated chloride channel. TMEM16A in human exhibits alternatively spliced exons (6b, 13 and 15), which confer important roles in the regulation of channel function. Mouse Tmem16a is reported to consist of 25 exons that code for a 956 amino acid protein.

Identification of histamine receptors and effects of histamine on murine and simian colonic excitability.

Background: Inflammatory responses can include recruitment of cells of hematopoietic origin to the tunica muscularis. These cells can secrete a variety of factors which can reset the gain of smooth muscle cells (SMC) and influence motor patterns. Histamine (H), a major mediator in inflammation, is released by mast cells and exerts diverse effects in SMC by binding to H receptors.

Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances.

Background And Purpose: Spontaneous electrical activity, termed slow waves, drives rhythmic, propulsive contractions in the smooth muscle of the oviduct (myosalpinx). Myosalpinx contractions cause egg transport through the oviduct. Agents that disrupt slow wave pacemaker activity will therefore disrupt myosalpinx contractions and egg transport.

Role of TREK-1 potassium channel in bladder overactivity after partial bladder outlet obstruction in mouse.

Purpose: Mouse models of partial bladder outlet obstruction cause bladder hypertrophy. Expression of a number of ion channels is altered in hypertrophic detrusor muscle, resulting in bladder dysfunction. We determined whether mechanosensitive TREK-1 channels are present in the murine bladder and whether their expression is altered in partial bladder outlet obstruction, resulting in abnormal filling responses.

Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles.

Interstitial cells of Cajal (ICC) generate pacemaker activity (slow waves) in gastrointestinal (GI) smooth muscles, but the mechanism(s) of pacemaker activity are controversial. Several conductances, such as Ca(2+)-activated Cl() channels (CaCC) and non-selective cation channels (NSCC) have been suggested to be involved in slow wave depolarization. We investigated the expression and function of a new class of CaCC, anoctamin 1 (ANO1), encoded by Tmem16a, which was discovered to be highly expressed in ICC in a microarray screen.

Cardiac-specific, inducible ClC-3 gene deletion eliminates native volume-sensitive chloride channels and produces myocardial hypertrophy in adult mice.

Native volume-sensitive outwardly rectifying anion channels (VSOACs) play a significant role in cell volume homeostasis in mammalian cells. However, the molecular correlate of VSOACs has been elusive to identify. The short isoform of ClC-3 (sClC-3) is a member of the mammalian ClC gene family and has been proposed to be a molecular candidate for VSOACs in cardiac myocytes and vascular smooth muscle cells.

Functional properties of murine bestrophin 1 channel.

Bestrophins form Ca2+-activated Cl- channels when they are expressed heterologously. Here we report the functional characterization of murine bestrophin 1 (mBest1). We isolated mBest1 transcript from mouse heart and analyzed the biophysical properties and expression of this channel protein using a tetracycline inducible system.

Functional role of CLC-2 chloride inward rectifier channels in cardiac sinoatrial nodal pacemaker cells.

A novel Cl(-) inward rectifier channel (Cl,ir) encoded by ClC-2, a member of the ClC voltage-gated Cl(-) channel gene superfamily, has been recently discovered in cardiac myocytes of several species. However, the physiological role of Cl,ir channels in the heart remains unknown. In this study we tested the hypothesis that Cl,ir channels may play an important role in cardiac pacemaker activity.

Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart.

Bestrophins are a novel family of proteins that encode calcium-activated chloride channels. In this study we establish that Bestrophin transcripts are expressed in the mouse and human heart. Native mBest3 protein expression and localization in heart was demonstrated by using a specific polyclonal mBest3 antibody.

Functional and molecular identification of pH-sensitive K+ channels in murine urinary bladder smooth muscle.

Objective: To examine the role of pH-sensitive K(+) channels in setting the resting membrane potential in murine bladder smooth muscle, as bladder contractility is influenced by the resting membrane potential, which is mainly regulated by background K(+) conductances.

Materials And Methods: Using conventional microelectrode recordings, isometric tension measurements, patch-clamp recordings, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, we assessed bladder smooth muscle cells and tissues.

Results: Acidic pH (pH 6.

Methionine and its derivatives increase bladder excitability by inhibiting stretch-dependent K(+) channels.

Background And Purpose: During the bladder filling phase, the volume of the urinary bladder increases dramatically, with only minimal increases in intravesical pressure. To accomplish this, the smooth muscle of the bladder wall must remain relaxed during bladder filling. However, the mechanisms responsible for the stabilization of bladder excitability during stretch are unclear.