Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of four multicenter clinical trials.

Importance: Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment.

Objective: This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients.

Design Setting And Participants: This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment ( = 1,479) or docetaxel single-agent treatment ( = 707).

Elucidation of the Application of Blood Test Biomarkers to Predict Immune-Related Adverse Events in Atezolizumab-Treated NSCLC Patients Using Machine Learning Methods.

Background: Development of severe immune-related adverse events (irAEs) is a major predicament to stop treatment with immune checkpoint inhibitors, even though tumor progression is suppressed. However, no effective early phase biomarker has been established to predict irAE until now.

Method: This study retrospectively used the data of four international, multi-center clinical trials to investigate the application of blood test biomarkers to predict irAEs in atezolizumab-treated advanced non-small cell lung cancer (NSCLC) patients.

Assessment of chimeric antigen receptor T cytotoxicity by droplet microfluidics in vitro.

Chimeric antigen receptor T (CAR-T) cells are cytotoxic T cells engineered to specifically kill cancer cells expressing specific target receptor(s). Prior CAR-T efficacy tests include CAR expression analysis by qPCR or ELISA, in vitro measurement of interferon-γ (IFNγ) or interleukin-2 (IL-2), and xenograft models. However, the in vitro measurements did not reflect CAR-T cytotoxicity, whereas xenograft models are low throughput and costly.

A Novel and Robust Single-cell Trapping Method on Digital Microfluidics.

Due to cell heterogeneity, the differences among individual cells are averaged out in bulk analysis methods, especially in the analysis of primary tumor biopsy samples from patients. To deeply understand the cell-to-cell variation in a primary tumor, single-cell culture and analysis with limited amount of cells are in high demand. Microfluidics has been an optimum platform to address the issue given its small reaction volume requirements.

Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel.

Cancer growth is usually accompanied by metastasis which kills most cancer patients. Here we aim to study the effect of cisplatin at different doses on breast cancer growth and metastasis. We used cisplatin to treat breast cancer cells, then detected the migration of cells and the changes of epithelial-mesenchymal transition (EMT) markers by migration assay, Western blot, and immunofluorescent staining.

Targeting NF-κB Signaling for Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling.

Genome-wide piggyBac transposon-based mutagenesis and quantitative insertion-site analysis in haploid Candida species.

Invasive fungal infections caused by Candida species are life threatening with high mortality, posing a severe public health threat. New technologies for rapid, genome-wide identification of virulence genes and therapeutic targets are urgently needed. Our recent engineering of a piggyBac (PB) transposon-mediated mutagenesis system in haploid Candida albicans provides a powerful discovery tool, which we anticipate should be adaptable to other haploid Candida species.

A digital microfluidic system with 3D microstructures for single-cell culture.

Despite the precise controllability of droplet samples in digital microfluidic (DMF) systems, their capability in isolating single cells for long-time culture is still limited: typically, only a few cells can be captured on an electrode. Although fabricating small-sized hydrophilic micropatches on an electrode aids single-cell capture, the actuation voltage for droplet transportation has to be significantly raised, resulting in a shorter lifetime for the DMF chip and a larger risk of damaging the cells. In this work, a DMF system with 3D microstructures engineered on-chip is proposed to form semi-closed micro-wells for efficient single-cell isolation and long-time culture.

Author Correction: Drug screening of cancer cell lines and human primary tumors using droplet microfluidics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Candida albicans gains azole resistance by altering sphingolipid composition.

In the original version of this Article, Haoping Liu, who conceptualized, designed and supervised the project and acquired funding, was inadvertently omitted from the author list. Furthermore, the affiliation of Jiaxin Gao and Haoping Liu with 'Department of Biological Chemistry, University of California, Irvine, CA 92697, USA' was omitted. Finally, funding from NIH grant GM117111, and contributions from Dr.

Candida albicans gains azole resistance by altering sphingolipid composition.

Fungal infections by drug-resistant Candida albicans pose a global public health threat. However, the pathogen's diploid genome greatly hinders genome-wide investigations of resistance mechanisms. Here, we develop an efficient piggyBac transposon-mediated mutagenesis system using stable haploid C.

A digital microfluidic system for loop-mediated isothermal amplification and sequence specific pathogen detection.

A digital microfluidic (DMF) system has been developed for loop-mediated isothermal amplification (LAMP)-based pathogen nucleic acid detection using specific low melting temperature (T) Molecular Beacon DNA probes. A positive-temperature-coefficient heater with a temperature sensor for real-time thermal regulation was integrated into the control unit, which generated actuation signals for droplet manipulation. To enhance the specificity of the LAMP reaction, low-T Molecular Beacon probes were designed within the single-stranded loop structures on the LAMP reaction products.

Drug screening of cancer cell lines and human primary tumors using droplet microfluidics.

Precision Medicine in Oncology requires tailoring of therapeutic strategies to individual cancer patients. Due to the limited quantity of tumor samples, this proves to be difficult, especially for early stage cancer patients whose tumors are small. In this study, we exploited a 2.

Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin.

Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target.

CDK phosphorylates the polarisome scaffold Spa2 to maintain its localization at the site of cell growth.

Polarisome is a protein complex that plays an important role in polarized growth in fungi by assembling actin cables towards the site of cell growth. For proper morphogenesis, the polarisome must localize to the right place at the right time. However, the mechanisms that control polarisome localization remain poorly understood.

Regulation of Rfa2 phosphorylation in response to genotoxic stress in Candida albicans.

Successful pathogens must be able to swiftly respond to and repair DNA damages inflicted by the host defence. The replication protein A (RPA) complex plays multiple roles in DNA damage response and is regulated by phosphorylation. However, the regulators of RPA phosphorylation remain unclear.

Rfa2 is specifically dephosphorylated by Pph3 in Candida albicans.

Rfa2 is a ssDNA (single-stranded DNA)-binding protein that plays an important role in DNA replication, recombination and repair. Rfa2 is regulated by phosphorylation, which alters its protein-protein interaction and protein-DNA interaction. In the present study, we found that the Pph3-Psy2 phosphatase complex is responsible for Rfa2 dephosphorylation both during normal G1-phase and under DNA replication stress in Candida albicans.

Crystal structure of the yeast metacaspase Yca1.

Yca1, the only metacaspase in Saccharomyces cerevisiae, is thought to be a clan CD cysteine protease that includes the caspase subfamily. Although yeast is a single cell eukaryote, it can undergo a cell death process reminiscent of apoptosis. Yca1 has been reported to play an important role in the regulation of such apoptotic process.

Pph3 dephosphorylation of Rad53 is required for cell recovery from MMS-induced DNA damage in Candida albicans.

The pathogenic fungus Candida albicans switches from yeast growth to filamentous growth in response to genotoxic stresses, in which phosphoregulation of the checkpoint kinase Rad53 plays a crucial role. Here we report that the Pph3/Psy2 phosphatase complex, known to be involved in Rad53 dephosphorylation, is required for cellular responses to the DNA-damaging agent methyl methanesulfonate (MMS) but not the DNA replication inhibitor hydroxyurea (HU) in C. albicans.

Relaxation of rat thoracic aorta by fibrate drugs correlates with their potency to disturb intracellular calcium of VSMCs.

Phenotypic modifications of vascular smooth muscle cells (VSMCs) contribute to pathological changes in atherosclerosis where modulation of intracellular calcium plays an important role. In this study, three fibrate drugs, namely gemfibrozil (Gem), fenofibric acid (Fa) and bezafibrate (Beza), were revealed to relax thoracic aorta associated with their potency to reduce intracellular calcium ([Ca²⁺]i) in cultured VSMCs. Relaxation effect of Gem, Fa and Beza was assayed on precontracted rat aortic rings.