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Pharmaceutical composition for treating renal clear cell carcinoma and application thereof

A technology for renal clear cell carcinoma and therapeutic drugs, applied in the field of medicine, can solve problems such as drug resistance that damages anti-cancer efficacy, and no research reports have been reported.

Active Publication Date: 2020-10-20
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But whether RCC also promotes the process of "browning" of adjacent adipose tissue and whether "browning" may impair anticancer efficacy and lead to drug resistance has not been well studied.
At the same time, whether tyrosine kinase inhibitors (TKIs) can promote the browning of adipose tissue around the kidneys has not been reported by other studies

Method used

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  • Pharmaceutical composition for treating renal clear cell carcinoma and application thereof
  • Pharmaceutical composition for treating renal clear cell carcinoma and application thereof
  • Pharmaceutical composition for treating renal clear cell carcinoma and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] In this example, it was discovered by analyzing the fat browning marker protein UCP1 in the cancer and paracancerous adipose tissue sections of patients with renal cancer clinically. The analysis results are as follows figure 1 As shown, the degree of browning of the proximal adipose tissue of RCC is stronger than that of the distal and subcutaneous adipose tissue, and there are significant differences. In addition, clinically, there is a significant difference in the expression of UCP1 protein between cancer and adjacent tumors in patients with RCC, and the adjacent adipose tissue is significantly higher than the distal end, which proves that RCC tumors can promote the browning of adjacent white adipose tissue. Previous studies have demonstrated that browned adipose tissue can secrete free fatty acids, which are conducive to tumor growth. Therefore, RCC can alter the tumor microenvironment by affecting the surrounding white adipose tissue.

Embodiment 2

[0032] This example verifies that the four most clinically used anti-tumor drugs for RCC (sunitinib, sorafenib, axitinib, and pazopanib) have the effect of promoting fat browning.

[0033] The specific experimental steps are as follows:

[0034] Step 1: Treat C3H10T1 / 2 cells with 1 μmol of four first-line anti-kidney cancer drugs for six days;

[0035] Step 2: After the cells have completed differentiation, detect the relative expression of UCP1 protein in the experimental group and the control group (such as figure 2 shown).

[0036] Depend on figure 2 It can be seen that the expression level of UCP1 in cells treated with four anticancer drugs was significantly higher than that in the control group, indicating that the clinical treatment of four anticancer drugs can cause browning of adjacent adipose tissue. Previous studies have demonstrated that browned adipose tissue can secrete free fatty acids, which are conducive to tumor growth. Therefore, this example proves tha...

Embodiment 3

[0038] This example verifies the therapeutic effects of four pharmaceutical compositions including the fat browning inhibitor H89 and first-line kidney cancer treatment drugs, wherein the four pharmaceutical compositions respectively include the following dosage components:

[0039] 1) Fat browning inhibitor H89 is used in combination with sunitinib, the dose of fat browning inhibitor is 1 mg / kg, and the dose of sunitinib is 10 mg / kg;

[0040] 2) Fat browning inhibitor H89 is used in combination with sorafenib, the dose of fat browning inhibitor is 1 mg / kg, and the dose of sorafenib is 10 mg / kg;

[0041] 3) Fat browning inhibitor H89 is used in combination with axitinib, the dose of fat browning inhibitor is 1 mg / kg, and the dose of axitinib is 10 mg / kg;

[0042] 4) Fat browning inhibitor H89 is used in combination with pazopanib, the dose of fat browning inhibitor is 1 mg / kg, and the dose of pazopanib is 10 mg / kg.

[0043] The specific experimental steps are as follows:

[...

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Abstract

The invention provides a pharmaceutical composition for treating the renal clear cell carcinoma and an application thereof. The pharmaceutical composition comprises a fat browning inhibitor and a first-line renal cancer treatment drug, wherein the first-line renal cancer treatment drug is selected from sunitinib, sorafenib, axitinib and pazopanib to form four combinations. The fat browning inhibitor in the pharmaceutical composition can improve the anti-cancer effects of the four kinds of first-line renal cancer treatment drugs, solve the problem that the four kinds of first-line renal cancertreatment drugs can cause white fat cell browning, further possibly damage the anti-cancer curative effect and cause drug resistance, reduce the treatment side effects of the drugs, and provide a newstrategy for treatment of the renal clear cell carcinoma.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a pharmaceutical composition for treating renal clear cell carcinoma and its application. Background technique [0002] Renal cell carcinoma (Renal cell cancer, RCC) has become one of the malignant tumors with the highest fatality rate, accounting for more than 2% of all human cancers, and the incidence of RCC continues to increase at a rate of about 2% per year. Based on histological and cytogenetic features, 80% of RCCs are subdivided into clear cell renal cell carcinoma (ccRCC). Tyrosine kinase inhibitors (TKIs) targeting VEGF receptors have shown efficacy in RCC, and sunitinib, sorafenib, axitinib and pazopanib have all been approved for clinical use First-line treatment. Unfortunately, emerging evidence suggests that a common limitation of TKI application in RCC is the development of drug resistance, which often leads to cancer recurrence. Long-term research efforts have identifie...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/404A61K31/44A61K31/4439A61K31/085A61K31/198A61K31/5025A61P13/12A61P35/00
CPCA61K45/00A61K31/404A61K31/44A61K31/4439A61K31/085A61K31/198A61K31/5025A61P13/12A61P35/00A61K2300/00
Inventor 刘军力
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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