CN113616649A - A combination drug for the treatment of liver cancer - Google Patents
A combination drug for the treatment of liver cancer Download PDFInfo
- Publication number
- CN113616649A CN113616649A CN202111063025.2A CN202111063025A CN113616649A CN 113616649 A CN113616649 A CN 113616649A CN 202111063025 A CN202111063025 A CN 202111063025A CN 113616649 A CN113616649 A CN 113616649A
- Authority
- CN
- China
- Prior art keywords
- sorafenib
- liver cancer
- avasimibe
- drug
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 201000007270 liver cancer Diseases 0.000 title claims abstract description 50
- 208000014018 liver neoplasm Diseases 0.000 title claims abstract description 47
- 238000011282 treatment Methods 0.000 title description 8
- 229940000425 combination drug Drugs 0.000 title 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims abstract description 56
- 229960003787 sorafenib Drugs 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 28
- 239000003937 drug carrier Substances 0.000 claims abstract description 3
- PTQXTEKSNBVPQJ-UHFFFAOYSA-N Avasimibe Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1CC(=O)NS(=O)(=O)OC1=C(C(C)C)C=CC=C1C(C)C PTQXTEKSNBVPQJ-UHFFFAOYSA-N 0.000 claims description 46
- 229950010046 avasimibe Drugs 0.000 claims description 38
- 230000035755 proliferation Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 8
- 230000001644 anti-hepatocarcinoma Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 23
- 206010028980 Neoplasm Diseases 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 241000036848 Porzana carolina Species 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 3
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 3
- 206010019695 Hepatic neoplasm Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000003235 crystal violet staining Methods 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000007928 intraperitoneal injection Chemical group 0.000 description 3
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 3
- -1 2, 6-diisopropylphenoxy Chemical group 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 2
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 2
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010019705 Hepatic pain Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 108091006625 SLC10A6 Proteins 0.000 description 1
- 206010041519 Spider naevus Diseases 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明提供了一种治疗肝癌的联合用药物，它含有用于同时或者分别给药的索拉非尼和阿伐麦布，以及药学上可接受的载体。本发明的索拉非尼和阿伐麦布联合用药物可以明显增强抗肝癌疗效，增加患者的用药依从性，为临床提供了一种新的选择。
The present invention provides a combined medicine for treating liver cancer, which contains sorafenib and avaimib for simultaneous or separate administration, and a pharmaceutically acceptable carrier. The combined medicine of sorafenib and avaimib of the present invention can obviously enhance the anti-hepatoma curative effect, increase the medication compliance of patients, and provide a new choice for clinical practice.
Description
Technical Field
The invention relates to the field of anti-cancer drugs, in particular to a combined drug for treating liver cancer.
Background
Liver cancer is a common malignant tumor in the digestive system, and is generally classified into primary liver cancer and secondary liver cancer. Primary liver cancer is classified into diffuse, lump, nodular and small cancer types, and clinical diseases often include liver pain, abdominal distension, asthenia, liver palms, spider nevus, jaundice and ascites. The secondary liver cancer is also called metastatic liver cancer, and malignant tumors generated in various parts of the whole body of a human body are accumulated to the liver to form the secondary liver cancer.
Sorafenib (chemical name: 4- (4-3- [ 4-chloro-3- (trifluoromethyl) phenyl ] ureidophenoxy) -N2-methylpyridine-2-carboxamide-4-tosylate), an oral multi-target kinase inhibitor, is a first-line treatment drug for advanced liver cancer, but sorafenib is only effective on 30% of patients with advanced liver cancer and only prolongs the median survival time for 3 months. Most patients are sensitive to sorafenib early, but after a period of treatment with sorafenib, the liver cancer recurs again and even progresses, the main reason for this being the development of sorafenib resistance. Although the curative effect of the sorafenib is limited by the drug resistance, the safety tolerance and the controllability of side effects of the sorafenib drug cause the sorafenib drug to be a first-line targeted drug for treating the liver cancer. In order to overcome the drug resistance of sorafenib, a combined drug scheme is urgently needed to be researched to enhance the curative effect of sorafenib.
Avasimibe (chemical name: N- (2, 6-diisopropylphenoxy) sulfonyl-2- (2,4, 6-triisopropylphenyl) acetamide) is an inhibitor of SOAT, and inhibits liver cancer by inhibiting synthesis of structural lipid and reducing fluidity of cell membrane, but unfortunately, avasimibe has very limited benefit on liver cancer patients.
At present, the combination of sorafenib and avasimibe for treating liver cancer does not exist.
Disclosure of Invention
In order to solve the problems, the invention provides a combined medicament for treating liver cancer, which comprises sorafenib and avasimibe for simultaneous or separate administration and a pharmaceutically acceptable carrier.
Further, the mass ratio of the sorafenib to the avasimibe is 5-15: 10-20.
Further, the mass ratio of sorafenib to avasimibe is 10: 15.
The invention also provides application of sorafenib and avasimibe in preparing a combined medicament for treating liver cancer.
Further, the mass ratio of the sorafenib to the avasimibe is 5-15: 10-20.
Further, the mass ratio of sorafenib to avasimibe is 10: 15.
Further, the liver cancer is primary liver cancer or secondary liver cancer.
Further, the liver cancer is a primary liver cancer.
Further, the drug is a drug that inhibits proliferation of liver cancer cells.
When the medicine is used for treating liver cancer, the combined medicine of sorafenib and avasimibe can obviously enhance the anti-liver cancer effect and increase the medication compliance of patients, thereby providing a new choice for clinic.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a statistical table of the change in the number of liver cancer cells (Control for Control group; Sora for sorafenib; Ava for avasimibe; FA for inhibition; CI for synergy index, where CI <1 for synergy, CI ═ 1 for simple additive effect, and CI >1 for antagonism; for significant difference p < 0.05; for very significant difference p < 0.01; for very significant difference p < 0.0001).
FIG. 2 is a graph showing the result of crystal violet staining (Control for Control; Sora for sorafenib; Ava for avasimibe)
FIG. 3 is a graph showing the effect of tumor inhibition (Control for Control group; Sora for sorafenib; Ava for avasimibe)
FIG. 4 tumor weight statistics (Control for Control; Sora for sorafenib; Ava for avasimibe; for very significant differences p < 0.01; for very significant differences p <0.001)
FIG. 5 tumor volume statistics (Control for Control; Sora for sorafenib; Ava for avasimibe; significant differences p < 0.05; very significant differences p <0.001)
Detailed Description
Experimental example 1 Sorafenib in combination with avasimibe inhibits hepatoma cells in vitro.
1. Experimental methods
1.1 cells for experiments
Liver cancer cell line: HepG2 liver cancer cell, HUH7 liver cancer cell
1.2 Experimental treatment: the hepatoma cell lines were treated with Control (Control), sorafenib (10 μ M), avasimibe (20 μ M), sorafenib (10 μ M) + avasimibe (20 μ M), respectively.
1.3, detection:
(1) CCK8 detection of cell number changes
After 3 days of experimental treatment, CCK8 is adopted to detect the proliferation condition of the liver cancer cells, and the result uses compusyn to calculate the synergy index.
(2) Observation of cell clone formation
After 7 days of experimental treatment, the number of clones was observed using crystal violet staining.
2. Results of the experiment
The results of the CCK8 testing the cell number change after different drug treatments are shown in FIG. 1, and can be seen from FIG. 1: the relative cell proliferation ratio of the sorafenib and avasimibe group is significantly lower than that of other groups. From fig. 1 it can be seen that: sorafenib and avasimibe in a molar ratio of 1: 2, the synergy indexes aiming at HepG2 liver cancer cells and HUH7 liver cancer cells are both less than 1, so that the sorafenib and the avasimibe can synergistically inhibit the proliferation of the liver cancer cells.
The crystal violet staining result is shown in figure 2, and it can be seen from figure 2 that the relative cell clone number of the sorafenib and avasimibe group is obviously less than that of other groups, so that the sorafenib and avasimibe group can be judged to be capable of effectively inhibiting the proliferation of liver cancer cells, and the anticancer effect of the sorafenib and avasimibe group is obviously better than that of sorafenib or avasimibe used alone.
3. Conclusion
Compared with the independent use of sorafenib or avasimibe, the combined use of sorafenib and avasimibe has better capability of inhibiting the proliferation of liver cancer cells in-vitro experiments, and the sorafenib and the avasimibe have synergistic effect.
Experimental example 2 Sorafenib and avasimibe in vivo inhibition of hepatoma cell proliferation
1. Experimental methods
1.1 constructing an animal model: mice were injected subcutaneously with HepG2 liver cancer cells (5.0X 10)6Individual cells).
1.2 drug configuration: sorafenib and avasimibe were dissolved with 20% PEG300, 5% Tween80, 5% DMSO and saline.
1.3 Experimental treatment: one week after injection, tumors were approximately 180mm in size3The mice are randomly divided into a control group, a sorafenib group, an avasimibe group and a sorafenib combined avasimian group, and each group comprises 8 mice. Control group (20% PEG300, 5% Tween80, 5% DMSO and normal saline, intraperitoneal injection, once a day), sorafenib group (10mg/kg, intraperitoneal injection, once a day); avasimibe group (15mg/kg, intraperitoneal injection, once a day); sorafenib (10mg/kg i.p., once daily) + avasimibe (15mg/kg i.p., once daily). Tumor diameter was measured every three days for 14 days. When the maximum diameter of the tumor reaches 1.5-2.0cm, the nude mice are killed by removing the neck, the tumor is stripped, the weight is measured, the tumor size is measured, and the volume is calculated: v ═ W (L ═ W)2) And/2, wherein L and W represent length and width.
2. Results
The tumor inhibition effect of each experimental group is shown in FIG. 3, the tumor weight statistics of each group are shown in Table 1 and FIG. 4, and the tumor volume statistics of each group are shown in Table 2 and FIG. 5.
TABLE 1 tumor weight changes
TABLE 2 tumor volume changes
As can be seen from tables 1-2 and FIGS. 3-5: in a nude mouse tumorigenesis experiment, compared with the sorafenib group or the avasimibe group which is used alone, the combination of the sorafenib and the avasimibe group can remarkably reduce the weight of the liver tumor and remarkably reduce the volume of the liver tumor.
3. Conclusion
In vivo experiments, sorafenib and avasimibe were mixed in a mass ratio of 10:15 compared with the single drug sorafenib or the single drug avasimibe, the combination can effectively inhibit the growth of liver cancer cells, reduce the weight and volume of tumors and has the synergistic effect.
In conclusion, the invention adopts the following steps that the molar ratio is 1: 2 (mass ratio 10: 22) is combined with avasimibe to be used for in vitro inhibition experiments of liver cancer cells, and the combination has obvious coordination and synergism effects, and because the in vivo experiments have more influence factors including drug absorption, drug metabolism, drug half-life period and the like, the in vivo and in vitro drug ratio can be different, and the invention adopts the following components in mass ratio of 10: the sorafenib and the avasimibe used for animal in-vivo inhibition experiments of liver tumors also show that the combination of the sorafenib and the avasimibe can remarkably inhibit the proliferation of liver cancer cells, and has good clinical application prospect.
Claims (9)
1. A combined medicine for treating liver cancer is characterized in that: it contains sorafenib and avasimibe for simultaneous or separate administration, and a pharmaceutically acceptable carrier.
2. The combination as set forth in claim 1, wherein: the mass ratio of the sorafenib to the avasimibe is 5-15: 10-20.
3. The combination as set forth in claim 2, wherein: the mass ratio of the sorafenib to the avasimibe is 10: 15.
4. use of sorafenib and avasimibe in the preparation of a combined medicament for treating liver cancer.
5. Use according to claim 4, characterized in that: the mass ratio of the sorafenib to the avasimibe is 5-15: 10-20.
6. Use according to claim 5, characterized in that: the mass ratio of the sorafenib to the avasimibe is 10: 15.
7. use according to claim 4, characterized in that: the liver cancer is primary liver cancer or secondary liver cancer.
8. Use according to claim 7, characterized in that: the liver cancer is primary liver cancer.
9. Use according to claim 5, characterized in that: the medicine is a medicine for inhibiting the proliferation of liver cancer cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111063025.2A CN113616649B (en) | 2021-09-10 | 2021-09-10 | A combination drug for the treatment of liver cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111063025.2A CN113616649B (en) | 2021-09-10 | 2021-09-10 | A combination drug for the treatment of liver cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113616649A true CN113616649A (en) | 2021-11-09 |
| CN113616649B CN113616649B (en) | 2022-12-09 |
Family
ID=78389776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111063025.2A Active CN113616649B (en) | 2021-09-10 | 2021-09-10 | A combination drug for the treatment of liver cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113616649B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103415286A (en) * | 2010-11-11 | 2013-11-27 | 阿克伦分子有限公司 | Compounds and methods for treating pain |
| US20140357676A1 (en) * | 2013-05-28 | 2014-12-04 | National Defense Medical Center | Pharmaceutical compositions and methods for treating cancer and biomarkers for drug screening |
| CN107320472A (en) * | 2017-08-09 | 2017-11-07 | 上海市第五人民医院 | A kind of pharmaceutical composition and its application for being used to treat liver cancer |
| CN109125324A (en) * | 2017-06-15 | 2019-01-04 | 北京蛋白质组研究中心 | Acyl-CoA: the new application of Cholesteryl acyltransferase 1 inhibitor |
| CN112494471A (en) * | 2020-12-14 | 2021-03-16 | 江南大学 | Application of cholesterol ester synthetase ACAT1 inhibitor in preparing medicine for preventing/treating non-alcoholic fatty liver disease |
-
2021
- 2021-09-10 CN CN202111063025.2A patent/CN113616649B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103415286A (en) * | 2010-11-11 | 2013-11-27 | 阿克伦分子有限公司 | Compounds and methods for treating pain |
| US20140357676A1 (en) * | 2013-05-28 | 2014-12-04 | National Defense Medical Center | Pharmaceutical compositions and methods for treating cancer and biomarkers for drug screening |
| CN109125324A (en) * | 2017-06-15 | 2019-01-04 | 北京蛋白质组研究中心 | Acyl-CoA: the new application of Cholesteryl acyltransferase 1 inhibitor |
| CN107320472A (en) * | 2017-08-09 | 2017-11-07 | 上海市第五人民医院 | A kind of pharmaceutical composition and its application for being used to treat liver cancer |
| CN112494471A (en) * | 2020-12-14 | 2021-03-16 | 江南大学 | Application of cholesterol ester synthetase ACAT1 inhibitor in preparing medicine for preventing/treating non-alcoholic fatty liver disease |
Non-Patent Citations (2)
| Title |
|---|
| LI GU1等: "Stabilization of FASN by ACAT1-mediated GNPAT acetylation promotes lipid metabolism and hepatocarcinogenesis", 《ONCOGENE》 * |
| 任正刚: "《肝癌》", 30 April 2009, 中国医药科技出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113616649B (en) | 2022-12-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA3222772A1 (en) | Erk1/2 and shp2 inhibitors combination therapy | |
| JP2014509657A5 (en) | ||
| CA3057969A1 (en) | Combination therapy | |
| KR20110028651A (en) | Combination of (A) phosphoinositide 3-kinase inhibitors and (iii) modulators of the RAS / RAF / MBE pathway | |
| WO2016014390A1 (en) | Compositions and methods for mek inhibitor combination therapy in the treatment of cancer | |
| Sung et al. | Combination of cytotoxic-differentiation therapy with 5-fluorouracil and phenylbutyrate in patients with advanced colorectal cancer | |
| BR112015012497B1 (en) | Pharmaceutical combinations and compositions, their uses, combined preparation, and commercial packaging | |
| JP2024125139A (en) | Antitumor pharmaceutical composition comprising azuvudine | |
| CN110755431B (en) | Application of desloratadine in the preparation of anti-liver cancer drugs | |
| CN113616649B (en) | A combination drug for the treatment of liver cancer | |
| Ravandi-Kashani et al. | Cutaneous ulcers associated with hydroxyurea therapy in myeloproliferative disorders | |
| CN110664807B (en) | A kind of pharmaceutical composition with synergistic anti-melanoma efficacy and application thereof | |
| CN116115623B (en) | Application of 2' -fucosyllactose as antitumor auxiliary drug | |
| WO2021023291A1 (en) | Use of proflavine in treatment of lung cancers | |
| CN111617081B (en) | Pharmaceutical composition combining substituted butenamide and mTOR inhibitor and application of pharmaceutical composition | |
| CN117357534A (en) | Use of pharmaceutical compositions containing retinoic acid in the preparation of medicaments for the treatment of hepatocellular carcinoma accompanied by abdominal metastasis | |
| WO2024221959A1 (en) | Oxidative stress inducer for triple-negative breast cancer cells and pharmaceutical composition for synergistically resisting triple-negative breast cancer | |
| WO2019034069A1 (en) | Antitumor combination drug and use thereof in preparation of anticancer drug | |
| JP7518183B2 (en) | Uses of Butylphthalide and Its Derivatives | |
| CN104398517A (en) | New application of pyrimethamine and medicinal composition for treating for tumor | |
| RU2678103C2 (en) | Antitumour drug containing antitumour platinum complex, and antitumour effect enhancer | |
| RU2005132175A (en) | COMBINED TREATMENT OF TUMORS, INCLUDING NEMORUBICINS AND RADIATION THERAPY | |
| JP2017226643A5 (en) | ||
| JP2017226643A (en) | Injectable composition for topical administration for anticancer treatment comprising quinine salt suspension | |
| CN107441076B (en) | Combined medicine for treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |