Unexpected sirolimus-stimulated airway hyperreactivity in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a multisystem disease affecting primarily women, characterised in the lung by proliferation of LAM cells, abnormal smooth muscle-like cells with dysfunctional tuberous sclerosis complex genes. This dysfunction results in activation of mechanistic target of rapamycin (mTOR), leading to LAM cell proliferation. Sirolimus (rapamycin) is the only United States Food and Drug Administration-approved treatment for pulmonary LAM, resulting in decreased LAM cell growth/size and stabilised lung function [1].

Effects of Sirolimus Treatment on Fetal Hemoglobin Production and Response to SARS-CoV-2 Vaccination: A Case Report Study.

The β-thalassemias are a group of monogenic hereditary hematological disorders caused by deletions and/or mutations of the β-globin gene, leading to low or absent production of adult hemoglobin (HbA). For β-thalassemia, sirolimus has been under clinical consideration in two trials (NCT03877809 and NCT04247750). A reduced immune response to anti-SARS-CoV-2 vaccination has been reported in organ recipient patients treated with the immunosuppressant sirolimus.

Glutaredoxin-1 promotes lymphangioleiomyomatosis progression through inhibiting Bim-mediated apoptosis via COX2/PGE2/ERK pathway.

Background: Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease, characterized by progressive cyst formation and respiratory failure. Clinical treatment with the mTORC1 inhibitor rapamycin could relieve partially the respiratory symptoms, but not curative. It is urgent to illustrate the fundamental mechanisms of TSC2 deficiency to the development of LAM, especially mTORC1-independent mechanisms.

Retracted: A Systematic Review of Lymphangioleiomyomatosis on Diagnosis and Molecular Mechanism.

[This retracts the article DOI: 10.1155/2021/6612776.].

Spontaneous pneumothoraces during pregnancy in patients with lymphangioleiomyomatosis.

Patients with lymphangioleiomyomatosis (LAM) are prone to developing spontaneous pneumothoraces (SPs). We aimed to characterize the burden of SPs during pregnancy in LAM, using a web-based survey. Among the 50 respondents, 12 (24%) had never been pregnant and 38 (76%) were pregnant at least once, resulting in a total of 80 pregnancies.

Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

Unlabelled: Perivascular epithelioid cell tumors (PEComa) are a large family of mesenchymal neoplasms, with variable clinical course. Evidence regarding treatment of advanced PEComas is scarce, with only one FDA-approved treatment available. The goals of this study were to provide data regarding systemic treatments for advanced PEComas and to identify biomarkers of prognostic relevance.

Cystic Lung Disease Presenting as Recurrent Non-traumatic Chylothorax: Case Report and a Mini-Review.

Malignancy and infections are the most common causes of recurrent chylothorax. Cystic lung disease, especially sporadic pulmonary lymphangioleiomyomatosis (LAM), is a rare condition that may manifest as recurrent chylothorax. We present a case of a 42-year female who presented with dyspnea on exertion secondary to recurrent chylothorax, requiring three thoracenteses within a few weeks.

Probability of sporadic lymphangioleiomyomatosis in women presenting with spontaneous pneumothorax.

Background: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare low-grade neoplasm of young women characterized by multiple pulmonary cysts leading to progressive dyspnea and recurrent spontaneous pneumothorax (SP). The diagnosis of S-LAM may be delayed by several years. To reduce this delay, chest computed tomography (CT) screening has been proposed to uncover cystic lung disease in women presenting with SP.

Lymphangioleiomyomatosis: where endocrinology, immunology and tumor biology meet.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease found almost exclusively in genetic females and caused by small clusters of smooth muscle cell tumors containing mutations in one of the two tuberous sclerosis genes (TSC1 or TSC2). Significant advances over the past 2-3 decades have allowed researchers and clinicians to more clearly understand the pathophysiology of LAM, and therefore better diagnose and treat patients with this disease. Despite substantial progress, only one proven treatment for LAM is used in practice: mechanistic target of rapamycin complex 1 (mTORC1) inhibition with medications such as sirolimus.

Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition.

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates.

Targeting Fibroblast-Endothelial Interactions in LAM Pathogenesis: 3D Spheroid and Spatial Transcriptomic Insights for Therapeutic Innovation.

Lymphangioleiomyomatosis (LAM) is a progressive lung disease with limited treatments, largely due to an incomplete understanding of its pathogenesis. Lymphatic endothelial cells (LECs) invade LAM cell clusters, which include HMB-45-positive epithelioid cells and smooth muscle α-actin-expressing LAM-associated fibroblasts (LAMFs). Recent evidence shows that LAMFs resemble cancer-associated fibroblasts, with LAMF-LEC interactions contributing to disease progression.

Rapidly evolving pelvic lymphangioleiomyomatosis (LAM) mimicking bilateral hydrosalpinx: report of a rare case and literature review.

Lymphangioleiomyomatosis (LAM) represents a rare neoplasm affecting almost exclusively women of reproductive age. This condition mainly affects the lungs, but extrapulmonary locations such as the pelvis and the retroperitoneum are possible. Clinical evaluation and ultrasound imaging are usually non-specific, and the diagnosis is obtained through surgical excision and histopathological examination.

Exploring bilateral pneumothorax leading to a rare diagnosis in a young lady.

Bilateral pneumothorax is a rare occurrence and vigilant clinical examination is mandatory to suspect that during the presentation. This case illustrates a young lady presented with bilateral pneumothorax, new identification of lung cysts and chylous pleural effusion leading to diagnosis of lymphangioleiomyomatosis.

Pulmonary Langerhans Cell Histiocytosis Masquerading as Lymphangioleiomyomatosis.

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon lung disease that affects young adults aged 20 to 40 years with current or prior history of smoking. The pathologic cell type in PLCH is a dendritic cell of the monocyte-macrophage line that resembles cutaneous Langerhans cells. This report presents the case of a 42-year-old woman with PLCH.

Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells.

Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that predominantly affects women. LAM cells carry mutations, causing mTORC1 hyperactivation and uncontrolled cell growth. mTORC1 inhibitors stabilize lung function; however, sustained efficacy requires long-term administration, and some patients fail to tolerate or respond to therapy.

Cell survival pathways targeted in rare lung disease affecting women.

Novel drug targets are identified in lymphangioleiomyomatosis (LAM), a rare disease in women. These targets focus on uterine transcription factors necessary for LAM cell survival.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion.

Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM.

Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model Via Induction of Apoptosis.

Tuberous sclerosis complex (TSC) tumors are presently incurable despite a cytostatic response to mTOR pathway inhibition because recurrence of disease occurs after treatment is discontinued. Here, we explored the hypothesis that inhibiting tyrosine kinase activity in mesenchymal lineage-specific platelet-derived growth factor receptor β (PDGFRβ) signaling in TSC tumors is cytocidal and attenuates tumorigenesis at significantly higher levels than treatment with an mTOR inhibitor. Rapamycin-induced versus tyrosine kinase inhibitor (TKI)-induced renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) tumor cells were comparatively analyzed using cell survival assays, RNA sequencing, and bioinformatics to distinguish tumoricidal mechanisms adopted by each drug type.

Long-term volume reduction in renal angiomyolipomas embolized by gelatin sponge particles with or without supplementary microcoil embolization.

Objective: To examine the effect of supplementary microcoil embolization on the long-term progression of angiomyolipomas embolized using gelatin sponge particles (GSPs).

Methods: This retrospective study included 29 unruptured angiomyolipomas in 25 patients, treated by complete embolization and radiological follow-up for ≥3 years. Embolization was performed using GSPs and supplementary microcoils.