A clinical evaluation of an organ culture system to predict patient response to cancer therapy.

Introduction: organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy.

Methods: A multicenter, prospective, single-arm observational trial.

Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA-Associated Pancreatic Cancer in the Clinical and Preclinical Setting.

Unlabelled: Germline BRCA-associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum of response to platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable response followed by acquired resistance (OS <36 months), and (iii) long-term responders (OS >36 months). Patient-derived xenografts (PDX) were generated from 25 patients with glBRCA PDAC at different clinical time points.

Targeted nanoparticles modify neutrophil function .

Neutrophils play critical roles in a broad spectrum of clinical conditions. Accordingly, manipulation of neutrophil function may provide a powerful immunotherapeutic approach. However, due to neutrophils characteristic short half-life and their large population number, this possibility was considered impractical.

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells.

Computer Vision Malaria Diagnostic Systems-Progress and Prospects.

Accurate malaria diagnosis is critical to prevent malaria fatalities, curb overuse of antimalarial drugs, and promote appropriate management of other causes of fever. While several diagnostic tests exist, the need for a rapid and highly accurate malaria assay remains. Microscopy and rapid diagnostic tests are the main diagnostic modalities available, yet they can demonstrate poor performance and accuracy.

Evaluation of the Parasight Platform for Malaria Diagnosis.

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs.

Computer-vision-based technology for fast, accurate and cost effective diagnosis of malaria.

Background: Microscopy has long been considered to be the gold standard for diagnosis of malaria despite the introduction of newer assays. However, it has many challenges like requirement of trained microscopists and logistic issues. A vision based device that can diagnose malaria, provide speciation and estimate parasitaemia was evaluated.

Systemic regulation of the age-related decline of pancreatic β-cell replication.

The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic factor found in the circulation of young mice is able to increase the proliferation rate of old pancreatic β-cells.

Ready, set, cleave: proteases in action.

Activity-based probes are small molecules that can be used to monitor enzyme activity by covalently binding to specific residues in the active site. In this issue of Chemistry & Biology, Lu and colleagues developed a specific fluorescent activity-based probe that targets the papain-like cysteine bacterial type III effector protease AvrPphB and used it to demonstrate the regulation of the protease secretion and pathogenesis.

Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels.

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo.

Glucose and aging control the quiescence period that follows pancreatic beta cell replication.

Pancreatic beta cell proliferation has emerged as the principal mechanism for homeostatic maintenance of beta cell mass during adult life. This underscores the importance of understanding the mechanisms of beta cell replication and suggests novel approaches for regenerative therapy to treat diabetes. Here we use an in vivo pulse-chase labeling assay to investigate the replication dynamics of adult mouse beta cells.

Pancreatic cells and their progenitors.

Both type 1 and type 2 diabetes patients would greatly benefit from transplantation of insulin-producing pancreatic beta cells; however, a severe shortage of transplantable beta cells is a major current limitation in the use of such therapy. Understanding the mechanisms by which beta cells are naturally formed is therefore a central challenge for modern pancreas biology, in the hope that insights will be applicable for regenerative cell therapy strategies for diabetes. In particular, the cellular origins of pancreatic beta cells pose an important problem, with significant basic and therapeutic implications.