Methionine (Met) is an essential sulfur amino acid (AA) limiting growth and is the precursor of cysteine (Cys), the rate-limiting factor in the synthesis of glutathione, and the main intracellular non-enzymatic antioxidant. This study aimed at determining the effects of limited supplies in Met and(or) Cys in early aspects of adipose tissue development and oxidative stress in differentiated adipocytes. Incremental reductions in Met (70, 40, and 0 µM) were compared with Met 100 µM (control dose) in porcine preadipocytes cultured in media without or with Cys (250 µM). In Cys-deprived media, both the absence (0 µM) and the lowest dose of Met (40 µM) reduced preadipocyte proliferation. Adding Cys in media only partly compensated for this decrease. On the opposite, mild Met deficiency (70 µM) did not alter preadipocyte proliferation in media without or with Cys. Strong Met deficiency (40 µM) also reduced differentiation and lipid accumulation into preadipose cells. Mild Met deficiency also reduced preadipocyte differentiation when Cys was present in the culture media, whereas in Cys-deprived media, percent of differentiated cell was similar and intracellular lipid content was slightly higher at Met 70 µM than at Met 100 µM. Finally, incremental reductions in Met in media with or without Cys lowered reactive oxygen species (ROS) production by differentiated cells. These results demonstrate the strong dependency of porcine adipogenesis to sulfur AA supplies. Strong Met deficiency decreases both proliferation and differentiation, whereas mild deficiency only alters differentiation.
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http://dx.doi.org/10.1007/s00726-016-2369-y | DOI Listing |
Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).
View Article and Find Full Text PDFAsia Pac J Clin Oncol
January 2025
Wellington Blood and Cancer Centre, Health New Zealand/Te Whatu Ora - Capital, Coast and Hutt Valley, Wellington, New Zealand.
Aim: Manatū Hauora, the Ministry of Health of New Zealand (NZ), published minimum standards for molecular testing of colorectal cancers (CRCs) in June 2018. These included mismatch repair (MMR) testing at diagnosis and BRAFV600E mutation analysis on newly diagnosed stage IV CRCs. This study aimed to determine the proportion of patients with CRC in the South Island of NZ with metastatic deficient mismatch repair (dMMR) CRC, the proportion of metastatic CRCs and dMMR CRCs that have a BRAFV600E mutation, and audit testing for BRAF mutations and appropriate referral to genetics services.
View Article and Find Full Text PDFJTO Clin Res Rep
January 2025
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown.
Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry).
Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis.
Mol Genet Metab Rep
March 2025
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Background: The current standard of care for infantile-onset Pompe disease (IOPD), a severe form of acid α-glucosidase enzyme activity deficiency is: (1) detection by newborn screening, (2) early initiation of intravenous enzyme replacement therapy (ERT) using recombinant human acid alpha-glucosidase (rhGAA), with higher doses of rhGAA increasingly used to improve clinical outcomes, and (3) immune tolerization induction (ITI) using to prevent anti-rhGAA antibody formation, with methotrexate (MTX), rituximab, and IVIG used for patients who are cross-reactive immunologic material negative (CRIM-) and monotherapy with MTX used in patients who are cross-reactive immunologic material positive (CRIM+).
Objectives/methods: A pilot study evaluates a dose-intensive therapy (DIT) using high-dose ERT (40 mg/kg/week) and more frequent exposure to ERT (i.e.
Nutrients
December 2024
Human Potential Centre, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 0632, New Zealand.
Background/objectives: The rise in chronic metabolic diseases has led to the exploration of alternative diets. The carnivore diet, consisting exclusively of animal products, has gained attention, anecdotally, for imparting benefit for inflammatory conditions beyond that possible by other restrictive dietary approaches. The aim was to assess the micronutrient adequacy of four versions of the carnivore diet against national nutrient reference values (NRVs).
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