Cost-Effectiveness of Axicabtagene Ciloleucel for Adult Patients With Relapsed or Refractory Follicular Lymphoma in the United States.

Objectives: The results of a recent single-arm trial (ZUMA-5) of axicabtagene ciloleucel (axi-cel) for relapsed/refractory (r/r) follicular lymphoma (FL) demonstrated high rates of durable response and tolerable toxicity among treated patients. To quantify the value of axi-cel compared with standard of care (SOC) to manage r/r FL patients who have had at least 2 prior lines of systemic therapy (3L+), a cost-effectiveness model was developed from a US third-party payer perspective.

Methods: A 3-state partitioned-survival cost-effectiveness model was developed with a lifetime horizon.

The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA.

Acute Promyelocytic Leukemia is caused by expression of the oncogenic Promyelocytic Leukemia (PML)-Retinoic Acid Receptor Alpha (RARA) fusion protein. Therapy with arsenic trioxide results in degradation of PML-RARA and PML and cures the disease. Modification of PML and PML-RARA with SUMO and ubiquitin precedes ubiquitin-mediated proteolysis.

Clinical outcomes in patients relapsed/refractory after ≥2 prior lines of therapy for follicular lymphoma: a systematic literature review and meta-analysis.

Background: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review.

Appraisals by Health Technology Assessment Agencies of Economic Evaluations Submitted as Part of Reimbursement Dossiers for Oncology Treatments: Evidence from Canada, the UK, and Australia.

Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC).

The Cost Effectiveness of Axicabtagene Ciloleucel Versus Best Supportive Care in the Treatment of Adult Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL) After Two or More Lines of Systemic Therapy in Canada.

Background And Objective: Axicabtagene ciloleucel (axi-cel) received marketing authorisation in Canada for the treatment of relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, and the clinical and economic value of axi-cel to patients and the healthcare system should be examined. The objective of this analysis is to determine, from societal and public healthcare payer perspectives, the cost effectiveness of axi-cel versus best supportive care for patients with relapsed or refractory large B-cell lymphoma in Canada.

Methods: A pharmacoeconomic model was developed and populated with clinical data derived from the ZUMA-1 and SCHOLAR-1 studies using a propensity score-matched comparison.

Cost-Effectiveness of Brexucabtagene Autoleucel versus Best Supportive Care for the Treatment of Relapsed/Refractory Mantle Cell Lymphoma following Treatment with a Bruton's Tyrosine Kinase Inhibitor in Canada.

For patients with Mantle Cell Lymphoma (MCL), there is no recognized standard of care for relapsed/refractory (R/R) disease after treatment with a Bruton's tyrosine kinase inhibitor (BTKi). Brexucabtagene autoleucel (brexu-cel) represents a promising new treatment modality in MCL. We explored whether brexu-cel was cost-effective for the treatment of R/R MCL.

Founder cell configuration drives competitive outcome within colony biofilms.

Bacteria can form dense communities called biofilms, where cells are embedded in a self-produced extracellular matrix. Exploiting competitive interactions between strains within the biofilm context can have potential applications in biological, medical, and industrial systems. By combining mathematical modelling with experimental assays, we reveal that spatial structure and competitive dynamics within biofilms are significantly affected by the location and density of the founder cells used to inoculate the biofilm.

Pharmacological rescue of impaired mitophagy in Parkinson's disease-related LRRK2 G2019S knock-in mice.

Parkinson's disease (PD) is a major and progressive neurodegenerative disorder, yet the biological mechanisms involved in its aetiology are poorly understood. Evidence links this disorder with mitochondrial dysfunction and/or impaired lysosomal degradation - key features of the autophagy of mitochondria, known as mitophagy. Here, we investigated the role of LRRK2, a protein kinase frequently mutated in PD, in this process in vivo.

Onwards and Upwards: A Systematic Survey of Economic Evaluation Methods in Oncology.

Introduction: The type of methods used in economic evaluations of health technology can lead to results that may influence decisions. Despite the potential impact on decision making, there is very little documentation of methods used in economic evaluation in oncology pertaining to key assumptions and extrapolation methods of survival benefits, especially in terms of survival analysis techniques and methods for extrapolation.

Objectives: The primary objectives of this study were to identify, examine, and describe the methods used in economic evaluations in oncology over a 10-year period, while secondary objectives included examining the use of identified methods across different geographic regions.

BIAFLOWS: A Collaborative Framework to Reproducibly Deploy and Benchmark Bioimage Analysis Workflows.

Image analysis is key to extracting quantitative information from scientific microscopy images, but the methods involved are now often so refined that they can no longer be unambiguously described by written protocols. We introduce BIAFLOWS, an open-source web tool enabling to reproducibly deploy and benchmark bioimage analysis workflows coming from any software ecosystem. A curated instance of BIAFLOWS populated with 34 image analysis workflows and 15 microscopy image datasets recapitulating common bioimage analysis problems is available online.

Novel Confocal-Laser-Scanning-Microscopy and conventional measures investigating eroded dentine following dentifrice dab-on and brushing abrasion.

Objectives: To validate novel non-contacting Confocal-Laser-Scanning-Microscopy (CLSM) methodology with conventional Contacting Profilometry (CP) measures investigating brushing or dab-on of stannous-fluoride dentifrice on early aggressive dentine erosion.

Methods: 75 polished human dentine samples were prepared and eroded in agitated 6% citric acid then randomly allocated into 5 intervention groups; artificial saliva control (1); controlled use of a pressure sensitive counter-rotating oscillatory powered toothbrush with sodium-fluoride NaF (2) or stannous-fluoride SnF (3), and dab-on application of NaF (4) or SnF (5). Samples underwent three cycles of intervention and 2-min agitated 6 % citric acid challenges.

Semi-automated quantitation of mitophagy in cells and tissues.

Mitophagy is a natural phenomenon and entails the lysosomal degradation of mitochondria by the autophagy pathway. In recent years, the development of fluorescent pH-sensitive mitochondrial reporters has greatly facilitated the monitoring of mitophagy by distinguishing between cytosolic mitochondria or those delivered to acidic lysosomes. We recently published the mito-QC reporter, which consists of a mitochondrial outer membrane-localised tandem mCherry-GFP tag.

Cross-species comparison of CAR-mediated procarcinogenic key events in a 3D liver microtissue model.

Characterisation of the mode of action (MOA) of constitutive androstane receptor (CAR)-mediated rodent liver tumours involves measurement 5 key events including activation of the CAR receptor, altered gene expression, hepatocellular proliferation, clonal expansion and increased hepatocellular adenomas/carcinomas. To test whether or not liver 3D microtissues (LiMTs) recapitulate CAR- mediated procarcinogenic key events in response to the prototypical CAR activator phenobarbital (PB) we performed hepatocyte proliferation (LI%) analysis in rat and human LiMTs using a microTMA technology in conjunction with integrated transcriptomics (microarray) and proteomics analysis. The rationale for this approach was that LiMTs containing parenchymal and non-parenchymal cells (NPCs) are more physiologically representative of liver and thus would generate data more relevant to the in vivo situation.

FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning.

The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis.

A comparative map of macroautophagy and mitophagy in the vertebrate eye.

Photoreception is pivotal to our experience and perception of the natural world; hence the eye is of prime importance for most vertebrate animals to sense light. Central to visual health is mitochondrial homeostasis, and the selective autophagic turnover of mitochondria (mitophagy) is predicted to play a key role here. Despite studies that link aberrant mitophagy to ocular dysfunction, little is known about the prevalence of basal mitophagy, or its relationship to general autophagy, in the visual system.

A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine.

A high throughput histology (microTMA) platform was applied for testing drugs against tumors in a novel 3D heterotypic glioblastoma brain sphere (gBS) model consisting of glioblastoma tumor cells, iPSC-derived neurons, glial cells and astrocytes grown in a spheroid. The differential responses of gBS tumors and normal neuronal cells to sustained treatments with anti-cancer drugs temozolomide (TMZ) and doxorubicin (DOX) were investigated. gBS were exposed to TMZ or DOX over a 7-day period.

Imaging of the Segregation of the 2 Chromosomes and the Cell Division Proteins of Reveals an Unexpected Role for MipZ.

Coordinating chromosome duplication and segregation with cell division is clearly critical for bacterial species with one chromosome. The precise choreography required is even more complex in species with more than one chromosome. The alpha subgroup of bacteria contains not only one of the best-studied bacterial species, , but also several species with more than one chromosome.

Phosphorylation of Parkin at serine 65 is essential for its activation .

Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination of damaged mitochondria via mitophagy. PINK1 phosphorylates ubiquitin at serine 65 (Ser65) and Parkin at an equivalent Ser65 residue located within its N-terminal ubiquitin-like domain, resulting in activation; however, the physiological significance of Parkin Ser65 phosphorylation in mammals remains unknown.

Economic Evaluation of Bevacizumab for Treatment of Platinum-Resistant Recurrent Ovarian Cancer in Canada.

Background: Ovarian cancer is a leading cause of cancer-related mortality. Although the disease is relatively rare, it carries a disproportionately large morbidity burden.

Objective: We conducted a cost-utility analysis from a Canadian public payer perspective to determine the cost effectiveness of bevacizumab, a newly available treatment option for recurrent ovarian cancer.

Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand.

Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues.

Strategic and practical guidelines for successful structured illumination microscopy.

Linear 2D- or 3D-structured illumination microscopy (SIM or3D-SIM, respectively) enables multicolor volumetric imaging of fixed and live specimens with subdiffraction resolution in all spatial dimensions. However, the reliance of SIM on algorithmic post-processing renders it particularly sensitive to artifacts that may reduce resolution, compromise data and its interpretations, and drain resources in terms of money and time spent. Here we present a protocol that allows users to generate high-quality SIM data while accounting and correcting for common artifacts.

Cost-effectiveness of EOB-MRI for Hepatocellular Carcinoma in Japan.

Purpose: The objective of the study was to evaluate the cost-effectiveness of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan compared with extracellular contrast media-enhanced MRI (ECCM-MRI) and contrast media-enhanced computed tomography (CE-CT) scanning.

Methods: A 6-stage Markov model was developed to estimate lifetime direct costs and clinical outcomes associated with EOB-MRI. Diagnostic sensitivity and specificity, along with clinical data on HCC survival, recurrence, treatment patterns, costs, and health state utility values, were derived from predominantly Japanese publications.

Regulation of membrane ruffling by polarized STIM1 and ORAI1 in cortactin-rich domains.

Cell motility and migration requires the reorganization of the cortical cytoskeleton at the leading edge of cells and extracellular Ca entry is essential for this reorganization. However the molecular nature of the regulators of this pathway is unknown. This work contributes to understanding the role of STIM1 and ORAI1 in the promotion of membrane ruffling by showing that phospho-STIM1 localizes at the leading edge of cells, and that both phospho-STIM1 and ORAI1 co-localize with cortactin (CTTN), a regulator of the cytoskeleton at membrane ruffling areas.