Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344348 | PMC |
| http://dx.doi.org/10.14814/phy2.13983 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Long-term neuropsychologic outcome of pre-emptive mTOR inhibitor treatment in children with tuberous sclerosis complex (TSC) under 4 months of age (PROTECT), a two-arm, randomized, observer-blind, controlled phase IIb national multicentre clinical trial: study protocol.
Orphanet J Rare Dis
January 2025
Division of Pediatric Epileptology, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University, Heidelberg, Germany.
Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits.
View Article and Find Full Text PDFA rare case of a malignant hepatic perivascular epithelioid cell tumor (PEComa) with aggressive progression following the relapse of renal pecoma despite everolimus therapy.
Clin J Gastroenterol
January 2025
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
A 55-year-old man with tuberous sclerosis complex (TSC) was diagnosed with left renal angiomyolipoma (AML), a group of perivascular epithelioid cell tumors called PEComas. He had received the mTOR inhibitor everolimus, which resulted in a complete response. However, a left renal mass relapsed in two years, followed by the occurrence of a hepatic mass five months later.
View Article and Find Full Text PDFSelective deletion of from mouse cerebellar Purkinje neurons drives sex-specific behavioral impairments linked to autism.
Front Behav Neurosci
December 2024
Department of Biology, Miami University, Oxford, OH, United States.
Article Synopsis
- There is a significant sex bias in autism spectrum disorder (ASD), with 80% of cases diagnosed in males, making it challenging to uncover the biological reasons behind this difference.
- Loss of function mutations leading to dysregulated mTORC1 signaling are prevalent in individuals with tuberous sclerosis (TSC), and over 50% of those with TSC are also diagnosed with ASD, indicating a strong genetic link.
- In experiments with mice, it was found that while motor coordination deficits are similar in both male and female mice, social interaction impairments are significantly worse in males, suggesting that certain behavioral issues in ASD may vary based on sex.
Lymphangioleiomyomatosis of the Pelvic Lymph Nodes Detected Incidentally During Surgical Staging of Gynecological Malignancies: Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution.
In Vivo
December 2024
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Background/aim: Lymphangioleiomyomatosis (LAM) belongs to the perivascular epithelioid cell tumor (PEComa) family. The relationship between LAM and tuberous sclerosis complex (TSC) is of particular concern in a subset of women with clinically occult LAM involving the pelvic lymph nodes. This study aimed to investigate the clinicopathological features of incidental nodal LAM detected during the surgical staging of gynecological tumors.
View Article and Find Full Text PDFIntroduction: Hereditary bleeding disorders stem from the absence or insufficient levels of particular clotting proteins, essential for facilitating coagulation in the clotting cascade. Among the most prevalent are hemophilia A (deficiency of Factor VIII), hemophilia B (deficiency of Factor IX), and von Willebrand disease. Management of pharmacoresistant epilepsy is more difficult in a patient with bleeding disorder due to increased risk of bleeding during surgery.
View Article and Find Full Text PDFWant 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!