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Medicine composition for treating neuroblastoma

A neuroblastoma and composition technology, applied in the field of pharmaceutical compositions for the treatment of neuroblastoma, can solve problems such as complete remission and low

Inactive Publication Date: 2016-06-15
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, CiE (cisplatin + etoposide) and CDV (cyclophosphamide + daunorubicin + vincristine) alternate chemotherapy regimen is currently the first-line chemotherapy regimen for neuroblastoma in the high-risk group, but complete remission ( CR) and very good partial response (VGPR) remain below 40%
[0004] Moreover, the therapeutic effect of traditional chemotherapy regimens on neuroblastoma and the patient's tolerance are close to the maximum, and it is urgent to explore a safer and more effective combination chemotherapy regimen based on molecularly targeted drugs

Method used

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  • Medicine composition for treating neuroblastoma
  • Medicine composition for treating neuroblastoma
  • Medicine composition for treating neuroblastoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Embodiment 1. Effect and molecular mechanism of NVP-BEZ235 on neuroblastoma cells

[0101] 1. CCK-8 method to detect the effect of NVP-BEZ235 on the proliferation of neuroblastoma

[0102] In order to investigate the effect and molecular mechanism of the PI3K / mTOR dual inhibitor NVP-BEZ235 on neuroblastoma cells, the inventors first treated the neuroblastoma cell line SHSY-5Y with NVP-BEZ235 at concentrations of 200, 500, and 1000 nM and SK-N-MC, the treatment time was 12h or 24h, and the effect of NVP-BEZ235 on the proliferation of neuroblastoma was detected by CCK-8 method.

[0103] It was found that NVP-BEZ235 had a significant inhibitory effect on the proliferation of neuroblastoma cell lines in a time- and dose-dependent manner, as shown in figure 1 A and figure 1 Shown in B.

[0104] 2. Detection of the inhibitory effect of NVP-BEZ235 on neuroblastoma cell lines by immunoblotting

[0105] Furthermore, the present inventors detected the effects of NVP-BEZ235 on...

Embodiment 2

[0108] Embodiment 2, the influence of NVP-BEZ235 on cell cycle

[0109] 1. Analysis of the effect of NVP-BEZ235 on the cell cycle of neuroblastoma cells by flow cytometry

[0110] In order to further explore the mechanism of the inhibitory effect of NVP-BEZ235 on the proliferation of neuroblastoma cell lines, flow cytometry was used to detect the effect of NVP-BEZ235 on the cell cycle.

[0111] The result is as figure 2 A and figure 2 As shown in B, after neuroblastoma cell lines SHSY-5Y and SK-N-MC were treated with 500 and 1000 nM NVP-BEZ235 for 24 hours, the number of cells in S phase and G2 / M phase was significantly down-regulated, but no sub-G1 population appeared.

[0112] 2. Western blot analysis of the protein levels of cyclinD1 and cyclinE in NVP-BEZ235-treated neuroblasts

[0113] Further, in order to clarify the effect of NVP-BEZ235 on the G0 / G1 phase arrest of neuroblasts, the inventors analyzed the protein levels of cyclinD1 and cyclinE in neuroblasts treated...

Embodiment 3

[0115] Example 3, NVP-BEZ235 and Rubescensine A have a synergistic effect

[0116] 1. CCK-8 method to detect the effect of NVP-BEZ235 on the proliferation of neuroblastoma

[0117] SHSY-5Y (A) and SK-N-MC (B) cells were treated with different concentrations of Rubescensine A for 24 hours, and CCK8 was used to detect the cell proliferation level.

[0118] The results showed that Rubescensine A had a significant inhibitory effect on the proliferation of neuroblastoma cell lines, and it was time- and dose-dependent, as shown in Figure 4 A and Figure 4 Shown in B.

[0119] 2. Determination of the synergistic effect of NVP-BEZ235 and Rubescensin A

[0120] The inhibitory effects of different formulations of NVP-BEZ235 and Rubescensine A on the proliferation of neuroblastoma cells SH-SY-5Y and SK-N-MC were detected. Add NVP-BEZ235 and Oridonin to the 96-well plate of cultured neuroblastoma cells SH-SY-5Y and SK-N-MC according to the addition amount listed in Table 1, treat for...

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Abstract

The invention relates to a medicine composition for treating neuroblastoma. According to the scheme, oridonin and NVP-BEZ235 are applied jointly to treat neuroblastoma; meanwhile, the invention provides a mixture or the medicine composition containing the oridonin and the NVP-BEZ235.

Description

technical field [0001] The invention belongs to the field of oncology, and more specifically, the invention relates to a pharmaceutical composition for treating neuroblastoma. Background technique [0002] Neuroblastoma (Neuroblastoma, NB) differs from most other tumors in that it occurs frequently in children. It is an embryonal tumor originating from the neural crest and composed of undifferentiated sympathetic nerve cells. Its incidence rate is about 1 / 100,000 children under the age of 15, and it is the most common malignant tumor in children under the age of 1 clinically. Due to the update and improvement of neuroblastoma diagnosis and treatment methods in recent years, the overall survival rate of neuroblastoma patients has been greatly improved, but the survival rate and quality of life of high-risk children have not been significantly improved. [0003] Due to the high degree of malignancy, early bone marrow and / or bone metastasis, and minimal residual disease (MRD) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K31/4745A61P35/00
CPCA61K31/352A61K31/4745A61K2300/00
Inventor 高丰厚张李迪刘珍郭佳慧卢静刘珊玲
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE