Background: Representing 15-20% of all breast cancer cases, triple negative breast cancer (TNBC) is diagnosed more frequently in reproductive-age women and exhibits higher rates of disease metastasis and recurrence when compared with other subtypes. Few targeted treatments exist for TNBC, and many patients experience infertility and endocrine disruption as a result of frontline chemotherapy treatment. While they are a promising option for less toxic therapeutic approaches, little is known about the effects of immune checkpoint inhibitors on reproductive and endocrine function.
Results: Our findings in a syngeneic TNBC mouse model revealed that therapeutically relevant immunotherapies targeting PD-1, LAG-3, and TIM-3 had no effect on the quality and abundance of ovarian follicles, estrus cyclicity, or hormonal homeostasis. Similarly, in a tumor-free mouse model, we found that ovarian architecture, follicle abundance, estrus cyclicity, and ovulatory efficiency remain unchanged by PD-1 blockade.
Conclusions: Taken together, our results suggest that immunotherapy may be a promising component of fertility-sparing therapeutic regimens for patients that wish to retain ovarian and endocrine function after cancer treatment.
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http://dx.doi.org/10.1101/2024.08.14.607933 | DOI Listing |
Am J Case Rep
December 2024
Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
BACKGROUND Limb-girdle muscular dystrophy recessive 1 (LGMDR1) is an autosomal recessive degenerative muscle disorder characterized by progressive muscular weakness caused by pathogenic variants in the CAPN3 gene. Desmoplastic small round cell tumors (DSRCT) are ultra-rare and aggressive soft tissue sarcomas usually in the abdominal cavity, molecularly characterized by the presence of a EWSR1::WT1 fusion transcript. Mouse models of muscular dystrophy, including LGMDR1, present an increased risk of soft tissue sarcomas.
View Article and Find Full Text PDFCell Death Differ
December 2024
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.
View Article and Find Full Text PDFSci Rep
December 2024
Central Laboratory, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215000, Jiangsu, China.
Yu-Ping-Feng-San (YPF) is a famous classical Chinese medicine formula known for its ability to boost immunity. YPF has been applied to enhance the immune status of tumor patients in clinical practice. However, there is still a lack of research on its immune regulatory effects and mechanisms in the tumor microenvironment.
View Article and Find Full Text PDFSci Rep
December 2024
School of Basic Medicine, Dali University, Dali, 671003, Yunnan, China.
Resolvin D1 (RvD1) is an endogenous anti-inflammatory mediator that modulates the inflammatory response and promotes inflammation resolution. RvD1 has demonstrated neuroprotective effects in various central nervous system contexts; however, its role in the pathophysiological processes of intracerebral hemorrhage (ICH) and the potential protective mechanisms when combined with exercise rehabilitation remain unclear. A mouse model of ICH was established using collagenase, and treatment with RvD1 combined with three weeks of exercise rehabilitation significantly improved neurological deficits, muscle strength, learning, and memory in ICH mice while reducing anxiety-like behavior.
View Article and Find Full Text PDFSci Rep
December 2024
School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China.
Microtextured microneedles are tiny needle-like structures with micron-scale microtextures, and the drugs stored in the microtextures can be released after entering the skin to achieve the effect of precise drug delivery. In this study, the skin substitution model of Ogden's hyperelastic model and the microneedle array and microtexture models with different geometrical parameters were selected to simulate and analyse the flow of the microtexture microneedle arrays penetrating the skin by the finite-element method, and the length of the microneedles was determined to be 200 μm, the width 160 μm, and the value of the gaps was determined to be 420 μm. A four-pronged cone was chosen as the shape of microneedles, and a rectangle was chosen as the shape of the drug-carrying microneedle.
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