AI Article Synopsis
Article Abstract
Background: Li-Fraumeni syndrome (LFS) is a highly penetrant autosomal dominant cancer predisposition disorder caused by germline pathogenic variants. Patients with LFS have increased oxidative phosphorylation capacity in skeletal muscle and oxidative stress in blood. Metformin inhibits oxidative phosphorylation, reducing available energy for cancer cell proliferation and decreasing production of reactive oxygen species that cause DNA damage. Thus, metformin may provide pharmacologic risk reduction for cancer in patients with LFS, but its safety in nondiabetic patients with germline pathogenic variants has not been documented.
Methods: This study assessed safety and tolerability of metformin in nondiabetic LFS patients and measured changes in metabolic profiles. Adult patients with LFS and germline variant received 14 weeks of metformin. Blood samples were obtained for measurement of serum insulin-like growth factor-1, insulin, and insulin-like growth factor binding protein 3. Hepatic mitochondrial function was assessed with fasting exhaled CO after ingestion of C-labeled methionine. Changes in serum metabolome were measured. All statistical tests were 2-sided.
Results: We enrolled 26 participants: 20 females and 6 males. The most common adverse events were diarrhea (50.0%) and nausea (46.2%). Lactic acidosis did not occur, and there were no changes in fasting glucose. Cumulative mean C exhalation was statistically significantly suppressed by metformin ( = .001). Mean levels of insulin-like growth factor binding protein 3 and insulin-like growth factor-1 were statistically significantly lowered ( = .02). Lipid metabolites and branched-chain amino acids accumulated.
Conclusions: Metformin was safe and tolerable in patients with LFS. It suppressed hepatic mitochondrial function as expected in these individuals. This study adds to the rationale for development of a pharmacologic risk-reduction clinical trial of metformin in LFS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746650 | PMC |
| http://dx.doi.org/10.1093/jncics/pkaa063 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical Analysis of Pediatric Acute Leukemias of Ambiguous Lineage: A Single Institution Retrospective Review.
J Pediatr Hematol Oncol
December 2024
From the Department of Pediatrics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Institutes of Health Science, Tianjin, China.
Acute leukemias of ambiguous lineage (ALAL) is a rare type of acute leukemia, referring to a group of disorders characterized by a combination of myeloid, lymphoid, or more lineages, whose incidence is significantly lower in children than adults. Here, we summarized the clinical features and outcomes of 36 pediatric ALAL patients in past 16 years. The patients diagnosed as ALAL based on the criteria of EGIL scoring system in 1998 (EGIL 1998) and/or the 2016 revisions to the WHO classification (WHO 2016) from January 1, 2005 to December 1, 2021 were included, respectively.
View Article and Find Full Text PDFFludarabine melphalan reduced intensity conditioning vs radiation-based myeloablative conditioning in patients undergoing allogeneic transplantation for acute myeloid leukemia with measurable residual disease.
Bone Marrow Transplant
December 2024
: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
Patients with AML and measurable residual disease (MRD) undergoing allogeneic hematopoietic cell transplantation (HCT) may benefit from myeloablative conditioning (MAC) when feasible to reduce relapse risk. Fludarabine-Melphalan (FluMel) is a common reduced intensity conditioning (RIC) regimen; however, data in MRD+ patients is sparse. We performed a retrospective review of AML patients who underwent their first HCT (2016-2021) without morphologic disease at City of Hope who had pre-transplant marrow evaluated for MRD using multicolor flow cytometry (MFC) and received radiation-based MAC or FluMel conditioning.
View Article and Find Full Text PDFTreatment of Vietnamese patients diagnosed with myelodysplastic neoplasms: Practical experience in a developing country.
Leuk Res Rep
November 2024
Department of Chemotherapy, National Institute of Hematology and Blood Transfusion, Hanoi 11312, Vietnam.
Background: Treatment of patients diagnosed with myelodysplastic neoplasms (MDS) is difficult and the outcome is still limited, especially in developing countries. We conducted this study in order to share some experience in treating patients diagnosed with MDS in developing countries.
Methods: This was a retrospective study that included 32 patients with newly MDS.
TP53 missense allele predisposing to high risk of breast cancer but not pediatric cancers.
J Natl Cancer Inst
December 2024
Hereditary Research Laboratory, Bethlehem University, Bethlehem, Palestine.
Pathogenic TP53 germline variants cause young-onset breast cancer and other cancers of the Li-Fraumeni syndrome (LFS) spectrum, but the clinical consequences of partial-loss-of function TP53 variants are incompletely understood. In the consecutive cohort of Palestinian breast cancer patients of the Middle East Breast Cancer Study (MEBCS), breast cancer risk among TP53 p. R181C heterozygotes was 50% by age 50 y and 81% by age 80 y.
View Article and Find Full Text PDFAdditional value of dynamic iodine concentration derived from dual-energy CT in larynx preservation decision following neoadjuvant chemotherapy.
Clin Radiol
November 2024
Department of Radiology, The First Hospital of Qinhuangdao, China.
Aim: To develop a larynx preservation (LP) score model to predict laryngectomy-free survival (LFS) in advanced laryngeal squamous-cell carcinoma (LSCC) with morphological response to neoadjuvant chemotherapy (NAC).
Materials And Methods: In this retrospective study, patients with advanced LSCC were included. All patients were classified into NAC response and non-response groups according RECIST.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!