Introduction: Metastases from renal cell carcinoma develop in various organs. However, the breadth of discrepancy in response to immune checkpoint inhibitors across tumor sites within the same individual remains unclear.
Patients And Methods: We reviewed 50 patients with metastatic renal cell carcinoma who had target lesions at multiple sites and received nivolumab monotherapy (n = 36) or nivolumab plus ipilimumab (n = 14). When the best overall response in tumor burden increased at one site but decreased at other sites, the response was defined as a dissociated response. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1, and patients who met the definition of dissociated response were categorized as dissociated response. The rate of dissociated response and prognosis were evaluated.
Results: Eight of 36 (22%) and 4 of 14 (29%) patients treated with nivolumab and nivolumab plus ipilimumab were categorized as having dissociated response, respectively. The median overall survival of the patients treated with nivolumab was 20.2 months for those with a partial response, 6.8 months for those with stable disease, and 13.2 months for those with progressive disease, while dissociated response was not reached. There was no significant difference in the median overall survival between patients categorized as having progressive disease and those with dissociates response (P = 0.224).
Conclusion: A certain proportion of patients with metastatic renal cell carcinoma show dissociated response when treated with immune checkpoint inhibitors. The prognosis of patients with dissociated response and progressive disease was not shown to be significantly different.
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New Phytol
January 2025
National Key Laboratory for Tea Plant Germplasm Innovation and Resource Utilization, Anhui Agricultural University, Hefei, 230036, China.
Glycosylation is a key modification that affects secondary metabolites under stress and is influenced by glycinebetaine (GB) to regulate plant stress tolerance. However, the complexity and detection challenges of glycosides hinder our understanding of the regulatory mechanisms of their metabolic interaction with GB during stress. A glycoside-specific metabolomic approach utilizing cone voltage-induced in-source dissociation was developed, achieving precise and high-throughput detection of glycosides in tea plants by narrowing the target ion range by 94.
View Article and Find Full Text PDFCurr Biol
January 2025
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Department of Ophthalmology and Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address:
Defects in retinal metabolism have been linked to the onset and progression of various retinal diseases. Herein, we provide a protocol for measuring bioenergetics in dissociated mouse retinal photoreceptors. We outline detailed instructions for obtaining morphologically intact and viable photoreceptor cells from adult mice and preparing the cells for metabolic analysis using a SeahorseXFe24 analyzer.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, TN, Italy; Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address:
Reduced expression of nucleolar genes induces stress and DNA damage. Here, we present a protocol to analyze DNA fragmentation at the single-cell level in Drosophila imaginal discs using an optimized alkaline comet assay. We describe steps for larvae development, tissue disaggregation, and single-cell dissociation.
View Article and Find Full Text PDFBiomacromolecules
January 2025
School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, U.K.
Enzymes are attractive as catalysts due to their specificity and biocompatibility; however, their use in industrial and biomedical applications is limited by stability. Here, we present a facile approach for enzyme immobilization within "all-enzyme" hydrogels by forming photochemical covalent cross-links between the enzyme glucose oxidase. We demonstrate that the mechanical properties of the enzyme hydrogel can be tuned with enzyme concentration and the data suggests that the dimeric nature of glucose oxidase results in unusual gel formation behavior which suggests a degree of forced induced dimer dissociation and unfolding.
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