NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice-Brief Report.

Objective: NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis.

Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project.

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used.

Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration.

Head and neck cancer patient images for determining auto-segmentation accuracy in T2-weighted magnetic resonance imaging through expert manual segmentations.

Purpose: The use of magnetic resonance imaging (MRI) in radiotherapy treatment planning has rapidly increased due to its ability to evaluate patient's anatomy without the use of ionizing radiation and due to its high soft tissue contrast. For these reasons, MRI has become the modality of choice for longitudinal and adaptive treatment studies. Automatic segmentation could offer many benefits for these studies.

Primary urethral cancer: treatment patterns and associated outcomes.

Objectives: To evaluate treatment patterns and associated outcomes of patients with urethral cancer.

Patients And Methods: After obtaining institutional review board approval we identified 165 patients treated for primary urethral cancer between 1956 and 2017. Treatment included monotherapy (surgery or radiation), dual therapy (surgery+radiation, surgery+chemotherapy, or chemotherapy+radiation) or triple therapy (surgery+radiation+chemotherapy).

Centrosome anchoring regulates progenitor properties and cortical formation.

Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex. In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex. However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown.

Modern treatments and future directions for newly diagnosed multiple myeloma patients.

Over the course of the past decade-plus, the therapy of newly diagnosed multiple myeloma has seen incredible advances in the domains of diagnostic evaluation, active medical therapy, and response evaluation. This manuscript reviews the evaluation and management of newly diagnosed active multiple myeloma, with a focus on major clinical trials and IMWG recommendations. The paper describes a current approach for the initial evaluation and workup for patients with putative active myeloma, with consideration towards potential MRD-directed therapeutic approaches and future clinical trials, and then discusses management with a focus on induction regimens with attention primarily to modern three and four-drug combinations for transplant-eligible and transplant-ineligible patients, and those with organ dysfunction.

CT images with expert manual contours of thoracic cancer for benchmarking auto-segmentation accuracy.

Purpose: Automatic segmentation offers many benefits for radiotherapy treatment planning; however, the lack of publicly available benchmark datasets limits the clinical use of automatic segmentation. In this work, we present a well-curated computed tomography (CT) dataset of high-quality manually drawn contours from patients with thoracic cancer that can be used to evaluate the accuracy of thoracic normal tissue auto-segmentation systems.

Acquisition And Validation Methods: Computed tomography scans of 60 patients undergoing treatment simulation for thoracic radiotherapy were acquired from three institutions: MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and the MAASTRO clinic.

A semi-mechanistic model based on glutathione depletion to describe intra-individual reduction in busulfan clearance.

Aim: To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing.

Methods: Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a semi-mechanistic model and compare it to a previously developed empirical model. The latter included an empirically estimated time effect, where the semi-mechanistic model included theoretical glutathione depletion.

The urachus revisited: multimodal imaging of benign & malignant urachal pathology.

The urachus is a fibrous tube extending from the umbilicus to the anterosuperior bladder dome that usually obliterates at week 12 of gestation, becoming the median umbilical ligament. Urachal pathology occurs when there is incomplete obliteration of this channel during foetal development, resulting in the formation of a urachal cyst, patent urachus, urachal sinus or urachal diverticulum. Patients with persistent urachal remnants may be asymptomatic or present with lower abdominal or urinary tract symptoms and can develop complications.

The impact of fluid optimisation before induction of anaesthesia on hypotension after induction.

Intra-operative hypotension is a known predictor of adverse events and poor outcomes following major surgery. Hypotension often occurs on induction of anaesthesia, typically attributed to hypovolaemia and the haemodynamic effects of anaesthetic agents. We assessed the efficacy of fluid optimisation for reducing the incidence of hypotension on induction of anaesthesia.

Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study.

Background: Preclinical data suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a possible treatment for EGFR mutation-positive lung cancers with MET-driven acquired resistance. Phase 1 safety data of savolitinib (also known as AZD6094, HMPL-504, volitinib), a potent, selective MET TKI, plus osimertinib, a third-generation EGFR TKI, have provided recommended doses for study. Here, we report the assessment of osimertinib plus savolitinib in two global expansion cohorts of the TATTON study.

Occupational exposures and odds of gastric cancer: a StoP project consortium pooled analysis.

Background: Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer.

Methods: We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project.

Clinical Trial Simulation To Optimize Trial Design for Fludarabine Dosing Strategies in Allogeneic Hematopoietic Cell Transplantation.

Optimal fludarabine exposure has been associated with improved treatment outcome in allogeneic hematopoietic cell transplantation, suggesting potential benefit of individualized dosing. A randomized controlled trial (RCT) comparing alternative fludarabine dosing strategies to current practice may be warranted, but should be sufficiently powered for a relevant end point, while still feasible to enroll. To find the optimal design, we simulated RCTs comparing current practice (160 mg/m ) to either covariate-based or therapeutic drug monitoring (TDM)-guided dosing with potential outcomes being nonrelapse mortality (NRM), graft failure, or relapse, and ultimately overall survival (covering all three aforementioned outcomes).

Understanding Long Noncoding RNA and Chromatin Interactions: What We Know So Far.

With the evolution of technologies that deal with global detection of RNAs to probing of lncRNA-chromatin interactions and lncRNA-chromatin structure regulation, we have been updated with a comprehensive repertoire of chromatin interacting lncRNAs, their genome-wide chromatin binding regions and mode of action. Evidence from these new technologies emphasize that chromatin targeting of lncRNAs is a prominent mechanism and that these chromatin targeted lncRNAs exert their functionality by fine tuning chromatin architecture resulting in an altered transcriptional readout. Currently, there are no unifying principles that define chromatin association of lncRNAs, however, evidence from a few chromatin-associated lncRNAs show presence of a short common sequence for chromatin targeting.

Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells.

6-Substituted amiloride derivatives as inhibitors of the urokinase-type plasminogen activator for use in metastatic disease.

The oral K+-sparing diuretic amiloride shows anti-cancer side-activities in multiple rodent models. These effects appear to arise, at least in part, through moderate inhibition of the urokinase-type plasminogen activator (uPA, K = 2.4 µM), a pro-metastatic trypsin-like serine protease that is upregulated in many aggressive solid malignancies.

Neuroendocrine Neoplasms of the Small Bowel and Pancreas.

The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood.

Focal Immunotherapy-Induced Pancreatitis Mimicking Metastasis on FDG PET/CT.

A 46-year-old man with metastatic lung adenocarcinoma was treated with pembrolizumab. FDG PET/CT was performed after 3 cycles of treatment and revealed a focal region of pancreatic tail enlargement with an SUVmax value of 7. Following treatment with corticosteroids and discontinuation of pembrolizumab, radiological resolution was observed, and a diagnosis of focal immunotherapy-induced pancreatitis was made.

Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons.

Axonal degeneration is a key pathology of neurodegenerative diseases, including hereditary spastic paraplegia (HSP), a disorder characterized by spasticity in the lower limbs. Treatments for HSP and other neurodegenerative diseases are mainly symptomatic. While iPSC-derived neurons are valuable for drug discovery and target identification, these applications require robust differentiation paradigms and rapid phenotypic read-outs ranging between hours and a few days.

An Assessment of Circulating Chromogranin A as a Biomarker of Bronchopulmonary Neuroendocrine Neoplasia: A Systematic Review and Meta-Analysis.

Background: Management of bronchopulmonary neuroendocrine neoplasia (NEN; pulmonary carcinoids [PCs], small-cell lung cancer [SCLC], and large cell neuroendocrine carcinoma) is hampered by the paucity of biomarkers. Chromogranin A (CgA), the default neuroendocrine tumor biomarker, has undergone wide assessment in gastroenteropancreatic neuroendocrine tumors.

Objectives: To evaluate CgA in lung NEN, define its clinical utility as a biomarker, assess its diagnostic, prognostic, and predictive efficacy, as well as its accuracy in the identification of disease recurrence.

A socio-cultural study of traditional healers role in African health care.

Background: There is a widely held view that a major cause of delay in diagnosis of cancer at an early stage in Africa is the fact that many patients consult traditional healers first and are often treated by them until curative treatment cannot be undertaken.

Purpose: This qualitative study aimed at identifying cancer patients who have used traditional healers and their traditional healers' understanding of cancer, its causes and treatment, patients' motivations for patronizing traditional healers and their opinion about collaboration between physicians of western medicine and traditional healers as part of overall health care system.

Methods: Ethical approval was obtained from the UI/UCH IRB.

Utility of a ready-to-use PCR system for neuroendocrine tumor diagnosis.

Background: Multigene-based PCR tests are time-consuming and limiting aspects of the protocol include increased risk of operator-based variation. In addition, such protocols are complex to transfer and reproduce between laboratories.

Aims: Evaluate the clinical utility of a pre-spotted PCR plate (PSP) for a novel multigene (n = 51) blood-based gene expression diagnostic assay for neuroendocrine tumors (NETs).