Application of NUP98 gene as glioma stem cell specific molecular marker and glioblastoma treatment and prognosis target

A technology for glioblastoma and glioma stem cells, which can be used in biochemical equipment and methods, microbial assay/test, recombinant DNA technology, etc., and can solve problems such as the lack of effective progress in clinical treatment plans

Pending Publication Date: 2022-04-22
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Glioma stem cells (Glioma Stem Cells, GSC) are considered to be the key to GBM treatment resistance and tumor recurrence, but clinical treatments targeting GSC alone or in combination have not made effective progress

Method used

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  • Application of NUP98 gene as glioma stem cell specific molecular marker and glioblastoma treatment and prognosis target
  • Application of NUP98 gene as glioma stem cell specific molecular marker and glioblastoma treatment and prognosis target
  • Application of NUP98 gene as glioma stem cell specific molecular marker and glioblastoma treatment and prognosis target

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Embodiment 1

[0025] Glioblastoma Stem Cell Acquisition and Culture: Glioblastoma tissue used in the experiments of this invention was obtained from redundant surgically resected specimens from Duke University patients and was neuropathologically reviewed according to an Institutional Review Board approved protocol (090401) Informed consent was obtained, and all patient studies were performed in accordance with the Declaration of Helsinki. GSC387 and GSC4121 are transferred through Duke University's Material Transfer Agreement. All GSCs were cultured in Neurobasal medium (Invitrogen) supplemented with B27 (Invitrogen) without vitamin A, supplemented with EGF and bFGF (20 ng / mL each; R&D Systems), sodium pyruvate and glutamax.

[0026] In vivo tumorigenesis model construction: All mouse in vivo tumorigenesis experiments were performed according to animal experimental protocols approved by the Institutional Animal Care and Use Committee of the University of California, San Diego. Viable GSCs...

Embodiment 2

[0060] Experimental results:

[0061] figure 1 Analysis revealed specific upregulation of NUP98 in GSCs and GBMs. figure 1 A. mRNA expression profiles of NPC genes in the TCGA GBM database. B. Pairwise analysis of NPC gene RNA sequences of GSCs and DGCs. C. Quantification of NUP98 mRNA levels by qRT-PCR in glioblastoma and normal brain tissues. D. Determination of NUP98 protein levels in five pairs of GSCs and DGCs from patient-derived glioblastoma models (T387, T4121, T456, GSC23, and T3028) by Western blotting, and TUBULIN protein as an internal control. E. The protein level of NUP98 in glioblastoma and normal brain tissue was evaluated by immunoblotting, and TUBULIN protein was used as an internal control. F. Immunofluorescent staining of NUP98 in GSCs or DGCs of human glioblastoma samples T387 and 4121.

[0062] figure 2 Regulation of GSCs growth and self-renewal for NUP98. figure 2A. Quantitative RT-PCR detection of NUP98 mRNA in 387 and 4121 GSCs expressing non-...

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Abstract

The invention discloses application of an NUP98 gene as a glioma stem cell specific molecular marker and a glioblastoma treatment and prognosis target spot, NUP98 regulation and control of DNA damage repair is realized by combining with a transcription factor P65 and regulating and controlling the transcriptional activity of P65, and NUP98 overexpression is related to low survival rate of brain tumor patients. The NUP89 expression level is used as the marker of glioblastoma, the diagnosis accuracy of the NUP89 as the marker of glioblastoma is 93%, the diagnosis specificity is 100%, and the sensitivity is 85.4%.

Description

technical field [0001] The invention belongs to the technical field, and specifically relates to the application of NUP98 gene as a molecular marker for diagnosing glioma stem cells and a target for treatment and prognosis. Background technique [0002] Glioblastoma (GBM) is the most malignant glioma among astrocytic tumors. Tumors are subcortical, with most growing throughout the supratentorial hemisphere. It grows infiltratively and often invades several lobes and deep structures. It can also spread to the contralateral cerebral hemisphere through the corpus callosum. The most common site of occurrence is the frontal lobe. Glioblastoma grows rapidly, and 70% to 80% of patients have a disease course of 3 to 6 months, and only 10% of patients have a disease course of more than 1 year. Those with a longer course of disease may evolve from low-grade astrocytomas. Due to the rapid growth of the tumor, extensive cerebral edema, and obvious symptoms of increased intracranial ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11
CPCC12Q1/6886C12Q2600/118C12Q2600/158Y02A50/30
Inventor 汪秀星慈书圣秦浩凯
Owner NANJING MEDICAL UNIV
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