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There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations.

Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRASG12Cinhibitor, has shown promising antitumour activity in patients with KRASG12C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG12C-mutated NSCLC.

Various methods have been proposed currently to detect amethopterin (ATP, a widely used anticancer drug that is also called methotrexate); however, a simple and low-cost electrochemical method coupled with high sensitivity is scarce. In this study, by using low-cost and readily available nanocarbon black (NCB), which has excellent conductivity and stable dispersion in water as well as large surface area, as electrode materials to modify a glassy carbon electrode (GCE), a simple, inexpensive and highly-sensitive electrochemical sensor was constructed based on NCB/GCE. The electrochemical behaviors of ATP at both NCB/GCE and GCE were studied; the results show that the peak current of ATP at NCB/GCE is extremely higher than that at the bare GCE. For sensing ATP with high sensitivity, various control conditions including accumulation time, pH values of the phosphate buffer solution and NCB amount were optimized. The quantitative testing results show that NCB/GCE presents excellent sensing performances with a wide linearity range from 0.01 to 10.0 μM and low limit of detection (4.0 nM) towards ATP. Moreover, the investigation in the reproducibility and stability as well as selectivity of NCB/GCE demonstrated that the related results are also satisfactory. It is thus simple and effective method for ATP analysis and has important applications.

Triggering receptor expressed on myeloid cell 2 (TREM2) signaling often drives opposing effects in traumatic versus demyelinating CNS disorders. Here, we identify two distinct phenotypes of microglia and infiltrating myeloid populations dependent on TREM2 expression levels at the acute stage and elucidate how they mediate the opposing effects of TREM2 in spinal cord injury (SCI) versus multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High TREM2 levels sustain phagocytic microglia and infiltrating macrophages after SCI. In contrast, moderate TREM2 levels sustain immunomodulatory microglia and infiltrating monocytes in EAE. TREM2-ablated microglia (purine-sensing phenotype in SCI and reduced immunomodulatory phenotype in EAE) drive transient protection at the acute stage of both disorders, whereas reduced phagocytic macrophages and lysosome-activated monocytes lead to contrasting neuroprotective and demyelinating effects in SCI versus EAE, respectively. Our study provides comprehensive insights into the complex roles of TREM2 in myeloid populations across diverse CNS disorders, which has crucial implications in devising TREM2-targeting therapeutics.

Mesenchymal stem cells (MSCs) have received considerable attention in recent years. Particularly exciting is the prospect that MSCs could be differentiated into specialized cells of interest, which could then be used for cell therapy and tissue engineering. MSCs derived from nonhuman primates could be a powerful tool for investigating the differentiation potential in vitro and in vivo for preclinical research. The purpose of this study was to isolate cynomolgus mesenchymal stem cells (cMSCs) from adult bone marrow and characterize their growth properties and multipotency. Mononuclear cells were isolated from cynomolgus monkey bone marrow by density-gradient centrifugation, and adherent fibroblast-like cells grew well in the complete growth medium with 10μM Tenofovir. cMSCs expressed mesenchymal markers, such as CD29, CD105, CD166 and were negative for hematopoietic markers such as CD34, CD45. Furthermore, the cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages under certain conditions, maintaining normal karyotype throughout extended culture. We also compared different methods (lipofection, nucleofection and lentivirus) for genetic modification of cMSCs and found lentivirus proved to be the most effective method with transduction efficiency of up to 44.6% and lowest level of cell death. The cells after transduction stably expressed green fluorescence protein (GFP) and maintained the abilities to differentiate down osteogenic and adipogenic lineages. In conclusion, these data showed that cMSCs isolated from cynomolgus bone marrow shared similar characteristics with human MSCs and might provide an attractive cell type for cell-based therapy in higher-order mammalian species disorder models.

Rezivertinib (BPI-7711) is a novel third-generation EGFRtyrosine kinase inhibitor selective for EGFR-sensitizing and T790M mutations. This study was designed to evaluate the safety, efficacy, and pharmacokinetics of rezivertinib for patients having advanced NSCLC with EGFRT790M mutation.

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Hu: Astellas Pharma, Inc.: Research Funding. Xie: Sinocelltech Ltd.: Current Employment, Current equity holder in publicly-traded company.

The study reports a rare case of primary paranasal sinus angiosarcoma with pulmonary metastases detected by 18F-FDG PET/CT. A 29-year-old woman presented with nasal congestion and rhinorrhea for 6 months. CT scanning showed a large mass in the right maxillary sinus, which had infiltrated the surrounding tissues. Subsequent evaluation by 18F-FDG PET/CT indicated numerous nodules in the lung, in addition to the paranasal sinus mass, which exhibited elevated FDG activity. Histologic examination after nasal endoscopic biopsy confirmed the diagnosis as primary paranasal sinus angiosarcoma with pulmonary metastases.