ABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) are being increasingly utilised in the front-line (1L) setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L) vascular endothelial growth factor-receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy after 1L ICI therapy. PATIENTS AND METHODS: This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists' review using Response Evaluation Criteria in Solid Tumours v1.1. Descriptive statistics and Kaplan-Meier method were used. RESULTS: Seventy patients were included in the analysis. Median age at mccRCC diagnosis was 59 years; 8 patients (11%) had international metastatic database consortium favourable-risk disease, 48 (69%) had intermediate-risk disease and 14 (20%) had poor-risk disease. As 1L therapy, 12 patients (17%) received anti-programmed death ligand-1 (PD-(L)1) monotherapy with nivolumab or atezolizumab, 33 (47%) received nivolumab plus ipilimumab and 25 (36%) received combination anti-PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib and cabozantinib. On 2L TKI therapy, one patient (1.5%) achieved a complete response, 27 patients (39.7%) a partial response and 36 patients (52.9%) stable disease. Median progression-free survival (mPFS) was 13.2 months (95% confidence interval: 10.1, NA). Forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment because of toxicity. CONCLUSIONS: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy after 1L ICI, we observed 2L antitumour activity and tolerance comparable to historical data for 1L TKI.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Immunotherapy/methods , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Female , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Protein Kinase Inhibitors/pharmacology , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
A series of double-fluorogenic siliconrhodamine probes were synthesized. These tetrazine-functionalized, membrane-permeable labels allowed site-specific bioorthogonal tagging of genetically manipulated intracellular proteins and subsequent imaging using super-resolution microscopy.
ABSTRACT
The diagnostic potential of large A beta-peptide binding particles (LAPs) in the cerebrospinal fluid (CSF) of Alzheimer's dementia (AD) patients and non-AD controls (nAD) was evaluated. LAPs were detected by confocal spectroscopy in both groups with high inter-individual variation in number. Molecular imaging by confocal microscopy revealed that LAPs are heterogeneous superaggregates that could be subdivided morphologically into four main types (LAP 1-4). LAP-4 type, resembling a 'large chain of pearls', was detected in 42.1% of all nAD controls but it was virtually absent in AD patients. LAP-4 type could be selectively removed by protein A beads, a clear indication that it contained immunoglobulins in addition to beta-amyloid peptides (A beta 1-42). We observed a close correlation between LAPs and immunoglobulin G (IgG) concentration in CSF in controls but not in AD patients. Double labeling of LAPs with anti-A beta and anti-IgG antibodies confirmed that LAP-4 type consisted of A beta and IgG aggregates. Our results assign a central role to the immune system in regulating A beta1-42 homeostasis by clustering this peptide in immunocomplexes.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/immunology , Antigen-Antibody Complex/cerebrospinal fluid , Autoantibodies/cerebrospinal fluid , Dementia/cerebrospinal fluid , Immunoglobulin G/cerebrospinal fluid , Peptide Fragments/immunology , Alzheimer Disease/immunology , Amyloid beta-Peptides/cerebrospinal fluid , Autoantibodies/classification , Biomarkers/cerebrospinal fluid , Case-Control Studies , Central Nervous System/immunology , Dementia/classification , Dementia/immunology , Humans , Immunoglobulin G/immunology , Peptide Fragments/cerebrospinal fluid , Reference ValuesABSTRACT
This study attempted to determine the validity of the Ertl Neural Efficiency Analyzer as a measure of intellectual ability by using NEA-Alpha and Neural Efficiency scores to predict collage grade point average (GPA) both alone and in combination with paper-and-pencil measures of intelligence for 22 male and 64 female college students. Results indicate that NEA-Alpha scores can predict GPA with moderate sucess and also that NEA-Alpha scores account for variability in grade point average not associated with paper-and-pencil tests.
Subject(s)
Alpha Rhythm , Individuality , Intelligence Tests , Adult , Dominance, Cerebral , Educational Measurement , Female , Humans , Male , Probability , PsychometricsABSTRACT
Learning studies have typically been analyzed using the mean learning our across trials. This study was designed to determine if probability learning dab could be described by a family of learning ewes and to identify ability and personality correlates of these curves. One hundred eighteen Ss participated in an 18-trial four-choice probability learning task. The intertribal matrix of intercorrelations was factored to ob6ain three reference lemming curves and the corresponding reference curve scores. Ability and personality variables correlated differentially with these scores. These results and others are discussed.
