The aim of this study was to compare a non-invasive 18F-fluoromisonidazole ([18F]FMISO) PET assessment of tumour hypoxia with invasive Eppendorf pO2 measurements in 150-1,500 mm3 C3H mammary carcinomas transplanted on the back of CDF1 mice. The tumour-bearing mice breathed either carbogen gas (95% oxygen, 5% CO2) or normal air during both examinations. Additional autoradiography was performed in separate tumours treated similarly. The PET [18F]FMISO examination significantly discriminated between tumours of carbogen and air-breathing mice. For the pO2 measurements, there was a significantly lower percentage of measurements below 2.5 mmHg for carbogen-treated mice compared with air-breathing mice. However, no direct correlation between the methods was seen. A correlation was found between tumour volume and Eppendorf estimates of tumour hypoxia for the animals breathing normal air, but no correlation was found between the PET endpoint and tumour volume. This may be due to low pO2 measurements obtained in necrotic tissue. Autoradiography confirmed lower [18F]FMISO uptake in tumours of carbogen-breathing animals compared with air-breathing animals, and demonstrated the heterogeneity of the tracer uptake in small compared with larger tumours.
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http://dx.doi.org/10.1080/02841860260088863 | DOI Listing |
Hepatology
January 2025
Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA.
Background Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.
Approach Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed.
Target Oncol
January 2025
Hematology-Oncology Service, Department of Medicine, Centre hospitalier de l'Université de Montréal (CHUM), 1000, rue Saint-Denis, Montreal, QC, Canada.
Background: BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.
Objective: The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.
Background: Psoriasis is a chronic, systemic, inflammatory skin disease, with increasing prevalence; however, few studies have reported real-world prescription patterns and healthcare burden.
Objectives: This retrospective, observational cohort study used statutory health insurance claims data (January 2014-December 2019) to estimate prevalence/incidence of moderate-to-severe psoriasis in Germany. Patient characteristics, treatment patterns/compliance, and healthcare resource utilization (HCRU)/costs were evaluated, focusing on apremilast and anti-interleukin (IL) and anti-tumor necrosis factor (TNF) biologics.
J Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
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