Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV cancer.

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus.

Griddient: a microfluidic array to generate reconfigurable gradients on-demand for spatial biology applications.

Biological tissues are highly organized structures where spatial-temporal gradients (e.g., nutrients, hypoxia, cytokines) modulate multiple physiological and pathological processes including inflammation, tissue regeneration, embryogenesis, and cancer progression.

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma.

Background: Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma.

Methods: In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×10 to 450×10 CAR-positive T cells) or one of five standard regimens.

Competitive SNP-LAMP probes for rapid and robust single-nucleotide polymorphism detection.

In this work, we developed a simple and robust assay to rapidly detect SNPs in nucleic acid samples. Our approach combines loop-mediated isothermal amplification (LAMP)-based target amplification with fluorescent probes to detect SNPs with high specificity. A competitive "sink" strand preferentially binds to non-SNP amplicons and shifts the free energy landscape to favor specific activation by SNP products.

A role for microfluidic systems in precision medicine.

Precision oncology continues to challenge the "one-size-fits-all" dogma. Under the precision oncology banner, cancer patients are screened for molecular tumor alterations that predict treatment response, ideally leading to optimal treatments. Functional assays that directly evaluate treatment efficacy on the patient's cells offer an alternative and complementary tool to improve the accuracy of precision oncology.

Role of the Skin Microenvironment in Melanomagenesis: Epidermal Keratinocytes and Dermal Fibroblasts Promote BRAF Oncogene-Induced Senescence Escape in Melanocytes.

is the most common mutation driver in melanoma. This mutation is known to cause a brief burst of proliferation followed by growth arrest and senescence, which prevent an uncontrolled cell proliferation. This phenomenon is known as oncogene-induced senescence (OIS) and OIS escape is thought to lead to melanomagenesis.

Microfluidic deep mutational scanning of the human executioner caspases reveals differences in structure and regulation.

The human caspase family comprises 12 cysteine proteases that are centrally involved in cell death and inflammation responses. The members of this family have conserved sequences and structures, highly similar enzymatic activities and substrate preferences, and overlapping physiological roles. In this paper, we present a deep mutational scan of the executioner caspases CASP3 and CASP7 to dissect differences in their structure, function, and regulation.

Secondary Medication Administration and IV Smart Pump Setup.

Secondary infusion by large-volume IV smart pump is used extensively in the acute care setting for one-time or intermittent administration of medications such as antibiotics, electrolyte replacements, and some oncology drugs. Consistent and accurate delivery of secondary medications requires a full understanding of the system and setup requirements. Unfortunately, it is not uncommon for nurses to find a secondary medication only partially administered when their programming should have resulted in a complete infusion.

Single-cell nucleic acid profiling in droplets (SNAPD) enables high-throughput analysis of heterogeneous cell populations.

Experimental methods that capture the individual properties of single cells are revealing the key role of cell-to-cell variability in countless biological processes. These single-cell methods are becoming increasingly important across the life sciences in fields such as immunology, regenerative medicine and cancer biology. In addition to high-dimensional transcriptomic techniques such as single-cell RNA sequencing, there is a need for fast, simple and high-throughput assays to enumerate cell samples based on RNA biomarkers.

Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion.

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood.

Elucidating cancer-vascular paracrine signaling using a human organotypic breast cancer cell extravasation model.

In cancer metastasis, extravasation refers to the process where tumor cells exit the bloodstream by crossing the endothelium and invade the surrounding tissue. Tumor cells engage in complex crosstalk with other active players such as the endothelium leading to changes in functional behavior that exert pro-extravasation effects. Most in vitro studies to date have only focused on the independent effects of molecular targets on the functional changes of cancer cell extravasation behavior.

Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability.

Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor populations present.

Autofluorescence Imaging of 3D Tumor-Macrophage Microscale Cultures Resolves Spatial and Temporal Dynamics of Macrophage Metabolism.

Macrophages within the tumor microenvironment (TME) exhibit a spectrum of protumor and antitumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to nondestructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models.

Development of a Microfluidic Array to Study Drug Response in Breast Cancer.

Luminal geometries are common structures in biology, which are challenging to mimic using conventional in vitro techniques based on the use of Petri dishes. In this context, microfluidic systems can mimic the lumen geometry, enabling a large variety of studies. However, most microfluidic models still rely on polydimethylsiloxane (PDMS), a material that is not amenable for high-throughput fabrication and presents some limitations compared with other materials such as polystyrene.

The Centers For Medicare And Medicaid Services Hospital Ratings: Pitfalls Of Grading On A Single Curve.

The star rating system for hospitals of the Centers for Medicare and Medicaid Services (CMS) pools all hospitals together and awards each institution one to five stars for quality, despite variation across hospitals in the numbers and types of measures they report. Thus, hospitals essentially are being evaluated differently, which affects the validity of quality comparisons. We considered the number and types of measures reported and the size of measure denominators to represent different forms of a "test," and we used data from the December 2017 star ratings to show that hospitals took one of three general "test forms.

Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells.

The EGFR pathway plays a critical role in head and neck squamous cell carcinoma (HNSCC). Targeted therapies against the EGFR are utilized as a treatment for HNSCCC. However, patient response is heterogeneous and molecular biomarkers are lacking to predict patient response.

Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131).

The centrosome, consisting of two centrioles surrounded by a dense network of proteins, is the microtubule-organizing center of animal cells. Polo-like kinase 4 (PLK4) is a Ser/Thr protein kinase and the master regulator of centriole duplication, but it may play additional roles in centrosome function. To identify additional proteins regulated by PLK4, we generated an RPE-1 human cell line with a genetically engineered "analog-sensitive" PLK4, which genetically encodes chemical sensitivity to competitive inhibition via a bulky ATP analog.

Evaluating natural killer cell cytotoxicity against solid tumors using a microfluidic model.

Immunotherapies against solid tumors face additional challenges compared with hematological cancers. In solid tumors, immune cells and antibodies need to extravasate from vasculature, find the tumor, and migrate through a dense mass of cells. These multiple steps pose significant obstacles for solid tumor immunotherapy and their study has remained difficult using classic models based on Petri dishes.