sirolimus

In parallel, suppression of anabolic signaling, particularly impairment of the insulin-like growth factor-1/Akt/mechanistic target of rapamycin complex 1 (mTORC1) pathway, has been reported, indicating a shift in muscle protein turnover toward a catabolic state. By distinguishing drug-induced muscle toxicity from cancer cachexia and other wasting conditions, we propose that skeletal muscle should be recognized as a clinically relevant but underestimated target organ of cisplatin toxicity. Improved understanding of these processes may support the development of strategies to preserve muscle mass and function during cancer chemotherapy.

P2, N=30, Not yet recruiting, AFT Pharmaceuticals, Ltd. | Initiation date: Apr 2026 --> Aug 2026

Emerging evidence also implicates LHX2 in metabolic-epigenetic circuits, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) and Wingless/Int-1 (Wnt)/β-catenin axes, as well as microRNA (miRNA) regulation. We also discuss therapeutic strategies targeting LHX2, including molecular engineering to overcome species barriers, and outline key knowledge gaps. A comprehensive understanding of LHX2-regulated networks holds promise for advancing regenerative medicine and enabling precision interventions in developmental disorders.

Drug response prediction suggested reduced sensitivity to platinum chemotherapy and epidermal growth factor receptor (EGFR) inhibitors but increased sensitivity to phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) inhibitors...The Glyco. marker system provides a potential framework for prognostic assessment and precision oncology strategies in LUAD.

Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis...Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification.

Pathway enrichment analysis suggested that the potential target genes of hsa-miR-103a-3p were mainly enriched in AMP-activated protein kinase, mechanistic target of rapamycin, tumor necrosis factor, insulin signaling, and cellular senescence pathways...These findings suggest that adult S. japonicum worms may alter the miRNA expression profile of hepatic stellate cells, and that hsa-miR-103a-3p may be associated with fibrogenic responses and may have potential relevance to hepatocellular carcinoma-related processes. However, this inference is based on correlative TCGA data and does not imply a causal role in schistosomiasis-associated hepatocarcinogenesis.

The functional roles of MALAT1 siRNA, miR-204-5p mimics/antagomirs, rapamycin, and 3-methyladenine (3-MA) on LC3B expression and autophagic activation were assessed by Western blot and immunofluorescence confocal microscopy for LC3B puncta formation... In HCF-aa subjected to RES, MALAT1 functions intracellularly as a competing endogenous RNA to putatively sequester miR-204-5p, thereby de-repressing LC3B expression and promoting autophagic activation. Concurrent exosomal secretion of MALAT1 may additionally serve as a paracrine signal to neighboring cells, though this requires future conditioned-media transfer experiments to confirm.

While mTOR inhibitor sirolimus, the only FDA approved drug for this disease, stabilizes lung function in most LAM patients, the drug does not eliminate LAM cells, underscoring a critical gap in our understanding of the tumor microenvironment and cellular heterogeneity that drive disease progression...Findings were validated through multimodal imaging technologies. Present work advances the field by providing the first high-resolution blueprint of the LAM niche microenvironment, revealing novel cell states and crosstalk that identify promising therapeutic targets.

KRAS mutations and p-ERK1/2 expression support a potential role of MAPK/ERK signaling in AOT pathogenesis. The absence of PIK3CA mutations despite p-mTOR expression may in part suggest mutation-independent activation of the PI3K/mTOR pathway. The lack of nuclear β-catenin accumulation may suggest that canonical Wnt signaling is less likely to significantly contribute to AOT tumorigenesis. Further studies with larger cohorts and investigations of additional molecules related to these pathways are warranted.

Sirolimus therapy was initiated 3 months later to reduce the risk of progression of residual lesions...Clinicians should systematically evaluate adults with angiomyolipoma for underlying TSC, even in the absence of overt neurological signs. Early recognition is essential to ensure appropriate surveillance and prevent potentially serious renal and systemic complications.

P1/2, N=15, Not yet recruiting, Massachusetts General Hospital

The results show that the core targets of NAR for spinal cord injury include estrogen receptor 1, AKT serine/threonine kinase 1, B-cell lymphoma 2, PPARG, MAPK8, mechanistic target of rapamycin, protein kinase cAMP-activated catalytic subunit alpha, and HRas proto-oncogene, GTPase...In summary, this study systematically predicts the key targets and signaling pathways through which NAR may act in SCI, providing a theoretical basis for future mechanistic and translational research. However, because the findings are based on computational analyses alone, further in vitro and in vivo validation is required.