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1.
J Clin Med ; 12(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37959191

RESUMO

Neurosurgeons evaluate MRI scans to document whether surgical treatment has reduced syrinx size. Manual measurement of syrinx volume is time-consuming and potentially introduces operator error and bias. Developing convenient semiautomated volumetric analysis methods may encourage their clinical implementation and improve syringomyelia monitoring. We analyzed 30 SPGR axial MRI scans from 15 pre- and postoperative Chiari I and syringomyelia patients using two semiautomated (SCAT and 3DQI) methods and a manual Cavalieri (CAV) method. Patients' spinal cord and syrinx volumes pre- and postoperatively were compared by paired t-test. A decrease in syrinx volume (mm3) after surgery was detected across all methods. Mean syrinx volume (± SD) measured by CAV (n = 30) was, preoperatively, 4515 mm3 ± 3720, postoperatively 1109 ± 1469; (p = 0.0004). SCAT was, pre, 4584 ± 3826, post, 1064 ± 1465; (p = 0.0007) and 3DQI was, pre, 4027 ± 3805, post, 819 ± 1242; (p = 0.001). 3DQI and CAV detected similar mean spinal cord volumes before (p = 0.53) and after surgery (p = 0.23), but SCAT volumes differed significantly (p = 0.005, p = 0.0001). The SCAT and 3DQI semiautomated methods recorded surgically related syrinx volume changes efficiently and with enough accuracy for clinical decision-making and research studies.

2.
Cells ; 12(21)2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37947640

RESUMO

Glioblastoma is the most common malignant primary brain tumor. The outcome is dismal, despite the multimodal therapeutic approach that includes surgical resection, followed by radiation and chemotherapy. The quest for novel therapeutic targets to treat glioblastoma is underway. FKBP38, a member of the immunophilin family of proteins, is a multidomain protein that plays an important role in the regulation of cellular functions, including apoptosis and autophagy. In this study, we tested the role of FKBP38 in glioblastoma tumor biology. Expression of FKBP38 was upregulated in the patient-derived primary glioblastoma neurospheres (GBMNS), compared to normal human astrocytes. Attenuation of FKBP38 expression decreased the viability of GBMNSs and increased the caspase 3/7 activity, indicating that FKBP38 is required for the survival of GBMNSs. Further, the depletion of FKBP38 significantly reduced the number of neurospheres that were formed, implying that FKBP38 regulates the self-renewal of GBMNSs. Additionally, the transient knockdown of FKBP38 increased the LC3-II/I ratio, suggesting the induction of autophagy with the depletion of FKBP38. Further investigation showed that the negative regulation of autophagy by FKBP38 in GBMNSs is mediated through the JNK/C-Jun-PTEN-AKT pathway. In vivo, FKBP38 depletion significantly extended the survival of tumor-bearing mice. Overall, our results suggest that targeting FKBP38 imparts an anti-glioblastoma effect by inducing apoptosis and autophagy and thus can be a potential therapeutic target for glioblastoma therapy.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Humanos , Camundongos , Apoptose , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo
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