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1.
Drug Resist Updat ; 76: 101113, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39053384

RESUMO

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.

2.
Front Neurol ; 13: 1046441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36845225

RESUMO

Myxoma is the most common type of benign cardiac tumor in adults, and it has a strong tendency to embolize or metastasize to distant organs. Patients with multiple brain metastases have rarely been seen in clinics; hence, standard treatment protocols for multimyxoma metastasis in the brain have not been established. We present the case of a 47-year-old female who had convulsions in the right hand and repeated seizures. Computed tomography revealed multiple tumor sites in her brain. Craniotomy was conducted to remove the tumor sites. However, recurrent brain tumors and unexpected cerebral infarctions occurred frequently shortly after the treatment because the cardiac myxoma had not been treated due to the patient's personal concerns. The myxoma was resected by gamma knife radiosurgery, and temozolomide was given prior to cardiac surgery. There has been no evidence of tumor recurrence from the 2 years following the surgery until the present. This case highlights the importance of prioritizing cardiac lesions over cerebral lesions; if a cerebral metastasis has been found, it is likely that the cardiac myxoma is already unstable, with high rates of spread and metastasis. Therefore, it is unwise to treat metastasis sites before the cardiac myxoma. Additionally, the case suggests that gamma knife radiosurgery combined with temozolomide is effective as treatment for multiple myxoma metastasis in the brain. Compared with conventional cerebral surgery, gamma knife radiosurgery is safer, causes less bleeding, and requires a shorter time for recovery.

3.
Biomed Opt Express ; 10(10): 5351-5361, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31646050

RESUMO

The attenuated total reflection spectroscopy system with the Si container attached on the prism has been demonstrated as an efficient technique to obtain the dielectric properties of living cells in the THz range. We proposed a method to determine the dielectric responses of living cells based on the combination of the single-interface and two-interface ATR models without cell thickness. The experimental results for living glial-like cells (PC12, SVG P12 and HMO6) showed the dielectric responses in the THz region were related significantly to cell number, intracellular fluid, and cell structure. Moreover, the glioma cells (C6 and U87) exhibited different dielectric properties compared with the glial-like cells, which could be one reason for the glioma tissue diagnosis using THz wave.

4.
Tissue Eng Regen Med ; 16(2): 177-189, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30989044

RESUMO

BACKGROUND: Nano-hydroxyapatite/polyamide 66 (nHA/PA66) is a composite used widely in the repair of bone defects. However, this material is insufficient bioactivity. In contrast, D-RADA16-RGD self-assembling peptide (D-RADA16-RGD sequence containing all D-amino acids is Ac-RADARADARADARADARGDS-CONH2) shows admirable bioactivity for both cell culture and bone regeneration. Here, we describe the fabrication of a favorable biomaterial material (nHA/PA66/D-RADA16-RGD). METHODS: Proteinase K and circular dichroism spectroscopy were employed to test the stability and secondary structural properties of peptide D-RADA16-RGD respectively. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the surface of these materials. Confocal laser scanning (CLS), cell counting kit-8 tests (CCK-8), alizarin red S staining, cell immunofluorescence analysis and Western blotting were involved in vitro. Also biosafety and bioactivity of them have been evaluated in vivo. RESULTS: Proteinase K and circular dichroism spectroscopy demonstrated that D-RADA16-RGD in nHA/PA66 was able to form stable-sheet secondary structure. SEM and TEM showed that the D-RADA16-RGD material was 7-33 nm in width and 130-600 nm in length, and the interwoven pore size ranged from 40 to 200 nm. CLS suggests that cells in nHA/PA66/D-RADA16-RGD group were linked to adjacent cells with more actin filaments. CCK-8 analysis showed that nHA/PA66/D-RADA16-RGD revealed good biocompatibility. The results of Alizarin-red S staining and Western blotting as well as vivo osteogenesis suggest nHA/PA66/D-RADA16-RGD exhibits better bioactivity. CONCLUSION: This study demonstrates that our nHA/PA66/D-RADA16-RGD composite exhibits reasonable mechanical properties, biocompatibility and bioactivity with promotion of bone formation.


Assuntos
Cimentos Ósseos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Durapatita/farmacologia , Nylons/farmacologia , Oligopeptídeos/farmacologia , Osteogênese/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Cimentos Ósseos/química , Regeneração Óssea/fisiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Durapatita/química , Endopeptidase K/química , Feminino , Fêmur/efeitos dos fármacos , Fêmur/lesões , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Nanocompostos/química , Nanocompostos/ultraestrutura , Nylons/química , Oligopeptídeos/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteogênese/fisiologia , Peptídeos/química , Estabilidade Proteica , Estrutura Secundária de Proteína , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície
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