Articles: signal-transducing-adaptor-proteins.
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Experimental hematology · Jan 2021
Generation of a lenalidomide-sensitive syngeneic murine in vivo multiple myeloma model by expression of CrbnI391V.
The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide are approved drugs for the treatment of multiple myeloma. IMiDs induce cereblon (CRBN) E3 ubiquitin ligase-mediated ubiquitination and degradation of Ikaros transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), which are essential for multiple myeloma. However, because of a single amino acid substitution of valine to isoleucine in mouse CRBN at position 391, mice are not susceptible to IMiD-induced degradation of neosubstrates. ⋯ BM. Luc.eGFP cells expressing murine CrbnI391V induced multiple myeloma in mice, and treatment with lenalidomide and pomalidomide significantly delayed tumor growth. This straightforward model provides a proof-of-concept for studying the effects of IMiDs in multiple myeloma in mice, which allows for in vivo testing of IMiDs and other CRBN E3 ligase modulators.
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Observational Study
Increased nuclear translation of YAP might act as a potential therapeutic target for NF1-related plexiform neurofibroma.
Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. ⋯ Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1-/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.
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Chinese medical journal · Dec 2020
Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy.
Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. ⋯ Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
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The roles of the Hippo‑Yes‑associated protein (YAP) pathway in lung injury and repair remain elusive. The present study examined the effects of systemic inhibition or stimulation of YAP activity on lung injury, repair and inflammation in a mouse model of lipopolysaccharide (LPS)‑induced lung injury. Mice were treated with or without YAP inhibitor, verteporfin, or with or without YAP stimulator, XMU‑MP‑1, and intraperitoneally injected with LPS (7.5 mg/kg). ⋯ Stimulation of YAP activity at the repair phase reversed all these processes. The results of the current study demonstrated that the Hippo‑YAP activity serves a protective role against endotoxemic lung injury. The Hippo‑YAP activity alleviated lung inflammation and injury at the injury phase and promoted inflammation resolution and lung repair at the repair phase.
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J. Pediatr. Hematol. Oncol. · Nov 2020
Case ReportsOncogenic GOPC-ROS1 Fusion Identified in a Congenital Glioblastoma Case.
Congenital glioblastoma (GBM) is a rare brain tumor of infancy. While histologically they resemble pediatric and adult GBM, growing evidence suggests a distinct molecular profile. ⋯ She underwent surgical resection, moderate-intensity chemotherapy without radiation, and remains disease-free 4 years from completion of therapy. While the frequency of this mutation is not known, the identification of this oncogenic driver may provide insight into the pathogenesis of GBM in this age group and may serve as a molecular target for select patients.