CN117701715A - Application of ODC1 and inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen - Google Patents
Application of ODC1 and inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen Download PDFInfo
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- CN117701715A CN117701715A CN202311759824.2A CN202311759824A CN117701715A CN 117701715 A CN117701715 A CN 117701715A CN 202311759824 A CN202311759824 A CN 202311759824A CN 117701715 A CN117701715 A CN 117701715A
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- breast cancer
- tamoxifen
- odc1
- inhibitor
- drug resistance
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- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 title claims abstract description 118
- 206010006187 Breast cancer Diseases 0.000 title claims abstract description 59
- 208000026310 Breast neoplasm Diseases 0.000 title claims abstract description 59
- 229960001603 tamoxifen Drugs 0.000 title claims abstract description 59
- 101001041245 Homo sapiens Ornithine decarboxylase Proteins 0.000 title claims abstract description 30
- 101000585693 Homo sapiens Mitochondrial 2-oxodicarboxylate carrier Proteins 0.000 title claims abstract description 29
- 102100021079 Ornithine decarboxylase Human genes 0.000 title claims abstract description 28
- 239000003112 inhibitor Substances 0.000 title claims abstract description 20
- 206010059866 Drug resistance Diseases 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title abstract description 18
- 238000003745 diagnosis Methods 0.000 title abstract description 9
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 12
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 239000003550 marker Substances 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003560 cancer drug Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 101100277160 Xenopus laevis odc1-a gene Proteins 0.000 claims 2
- 230000035755 proliferation Effects 0.000 abstract description 13
- 238000011160 research Methods 0.000 abstract description 5
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 abstract description 4
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 abstract description 4
- 229960003104 ornithine Drugs 0.000 abstract description 4
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 abstract description 3
- 238000002648 combination therapy Methods 0.000 abstract description 3
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 230000002018 overexpression Effects 0.000 abstract description 2
- 230000006907 apoptotic process Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 4
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 108090000672 Annexin A5 Proteins 0.000 description 3
- 102000004121 Annexin A5 Human genes 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 2
- 102000007594 Estrogen Receptor alpha Human genes 0.000 description 2
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 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 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- IRDDSLZMDLOSKG-UHFFFAOYSA-N 2-(difluoromethylamino)-1,7-dihydropurin-6-one Chemical compound FC(F)NC=1NC(C=2NC=NC=2N=1)=O IRDDSLZMDLOSKG-UHFFFAOYSA-N 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000007983 brain glioma Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000010293 colony formation assay Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000013038 irreversible inhibitor Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- -1 ornithine small molecule Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
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Abstract
The invention relates to the technical field of biological pharmacy, in particular to ODC1 and application of an inhibitor thereof in diagnosis and treatment of drug resistance of tamoxifen of breast cancer, and the invention discovers that the ODC1 is over-expressed in the drug resistant breast cancer cells of tamoxifen, so that the over-expression of the ODC1 can be used as a marker for judging or predicting the drug resistance of the tamoxifen of the breast cancer; in addition, the research of the invention discovers that the ODC1 inhibitor DFMO can obviously inhibit proliferation of ER alpha positive breast cancer cells and other moxifene resistant breast cancer cells when being used as a single medicament or combined with tamoxifen. Therefore, the ornithine metabolism related gene ODC1 is used as a diagnosis and prediction marker of the drug resistance of the tamoxifen of the breast cancer, and the combination therapy of the ODC1 inhibitor DFMO and the tamoxifen has great application value in the diagnosis and treatment of the drug resistance of the breast cancer of the tamoxifen.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to ODC1 and application of an inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen.
Background
Breast cancer is one of the most frequently occurring malignant tumors of women today, more than 70% of breast cancer patients are positive for estrogen receptor (ER alpha), tamoxifen is used as the most main endocrine treatment drug for ER alpha positive breast cancer patients, and about one third of patients can generate tamoxifen drug resistance along with the prolonging of the service life, and recurrent metastasis caused by the tamoxifen drug resistance is an important factor of death of breast cancer patients. Thus, revealing key molecules that induce tamoxifen resistance in ERα -positive breast cancers and developing new strategies for treatment of tamoxifen-resistant breast cancers are significant for maintaining female life health.
A large number of researches show that arginine/ornithine metabolic pathway is abnormally activated in various malignant tumors, and polyamine small molecules such as arginine/ornithine small molecule metabolite putrescine, spermine and the like can obviously promote the malignant progress of the tumors. Difluoromethylguanine (DFMO) as an irreversible inhibitor of ornithine decarboxylase ODC1 can significantly inhibit the biosynthesis of small polyamine molecules, thereby inhibiting tumor progression. DFMO and combination therapies containing DFMO have been developed in clinical studies on various malignancies such as brain glioma, small cell lung cancer, hodgkin lymphoma, and digestive tract tumors, and DFMO exhibits positive anticancer effects on various malignancies.
Disclosure of Invention
In order to overcome the defects and shortcomings in the prior art, the invention aims to provide ODC1 and application of an inhibitor thereof in drug resistance diagnosis and treatment of breast cancer tamoxifen.
The aim of the invention is achieved by the following technical scheme: use of ODC1 as a marker for the preparation of a reagent for diagnosing breast cancer tamoxifen resistance.
The other object of the invention is achieved by the following technical scheme: use of an ODC1 inhibitor in the manufacture of a medicament for breast cancer.
Preferably, the ODC1 inhibitor is DFMO.
Preferably, the breast cancer is erα positive breast cancer.
The invention also aims at realizing the following technical scheme: use of an ODC1 inhibitor for the manufacture of a medicament for improving the resistance of a patient to breast cancer.
Preferably, the ODC1 inhibitor is DFMO.
Preferably, the breast cancer drug resistance refers to breast cancer tamoxifen drug resistance.
Still another object of the present invention is achieved by the following technical scheme: application of ODC1 inhibitor and tamoxifen in preparing medicines for breast cancer.
Preferably, the ODC1 inhibitor is DFMO.
Preferably, the breast cancer is erα positive breast cancer.
The invention has the beneficial effects that: according to the invention, the research discovers that the ODC1 is over-expressed in the tamoxifen resistant breast cancer cells, so that the over-expression of the ODC1 can be used as a marker for judging or predicting the drug resistance of the breast cancer tamoxifen; in addition, the research of the invention discovers that the ODC1 inhibitor DFMO can obviously inhibit proliferation of ER alpha positive breast cancer cells and other moxifene resistant breast cancer cells when being used as a single medicament or combined with tamoxifen. Therefore, the ornithine metabolism related gene ODC1 is used as a diagnosis and prediction marker of the drug resistance of the tamoxifen of the breast cancer, and the combination therapy of combining DFMO and the tamoxifen has great application value in the diagnosis and treatment of the drug resistance of the breast cancer of the tamoxifen.
Drawings
FIG. 1 shows the measurement of the mRNA expression level of ODC1 of the present invention in tamoxifen-sensitive cell MCF-7 and drug-resistant cell MCF-7 TAMR.
FIG. 2 is a graph and statistical graph of the effect of the cloning of the present invention on the proliferation of MCF-7 cells, wherein A and B are DFMO, tamoxifen, alone or in combination, respectively; c and D are cell and statistical graphs of the effect of DFMO, tamoxifen, alone or in combination, on MCF-7TAMR cell proliferation, respectively.
FIG. 3 shows the detection of proliferation changes of tamoxifen-resistant breast cancer cells by CCK8 proliferation assay of the present invention.
FIG. 4 is an annexin V/PI apoptosis assay of the invention for detecting apoptosis changes in tamoxifen resistant breast cancer cells.
Detailed Description
The present invention is further described below with reference to examples and fig. 1-4 for the purpose of facilitating understanding of those skilled in the art, and the description of the embodiments is not intended to limit the invention.
Embodiment one: ODC1 was significantly elevated in tamoxifen resistant breast cancer cells.
Establishing a tamoxifen-resistant breast cancer cell research model MCF7TAMR by using an tamoxifen-sensitive ERalpha positive breast cancer cell line MCF7, and detecting the expression of ODC1mRNA by using a fluorescence quantitative PCR method under the condition that tamoxifen exists or does not exist. The experimental results are shown in fig. 1, and the results show that: ODC1 expression was significantly elevated in tamoxifen resistant breast cancer cells.
Embodiment two: DFMO in combination with tamoxifen significantly inhibited proliferation of era positive breast cancer cells.
Treatment of tamoxifen sensitive cells MCF-7 and tamoxifen resistant cells MCF-7TAMR with tamoxifen alone or DFMO, and treatment of MCF-7 breast cancer cells and their resistant cells MCF-7TAMR with the combination of the above two drugs, the effect of the above treatments on proliferation of both cells was examined using a colony formation assay. The experimental results are shown in fig. 2, and the results show that: treatment of tamoxifen alone only partially inhibits proliferation of MCF-7 cells, and has no inhibitory effect on tamoxifen resistant cells MCF-7TAMR at all; the DFMO alone treatment can obviously inhibit the proliferation of MCF-7 cells and other moxifene resistant cells, and shows stronger inhibition effect on two cells after combining with tamoxifen.
Embodiment III: CCK8 cell proliferation experiment for detecting proliferation change of tamoxifen-resistant breast cancer cells
In order to further verify the inhibition effect of DFMO on tamoxifen-resistant breast cancer, the invention further utilizes a CCK8 cell proliferation detection kit to detect the influence of DFMO on the proliferation and apoptosis of the breast cancer tamoxifen-resistant cells, which are used alone or in combination with tamoxifen. The CCK8 proliferation assay results are shown in fig. 3, which shows that: the DFMO alone treatment can obviously inhibit the proliferation of MCF-7 tamoxifen resistant cells, and the combination tamoxifen treatment shows stronger proliferation inhibition effect on tamoxifen resistant breast cancer cells.
Embodiment four: annexin V/PI flow apoptosis experiment for detecting apoptosis change of tamoxifen-resistant breast cancer cells
In order to further verify the inhibition effect of DFMO on tamoxifen-resistant breast cancer, the invention further utilizes an annexin V/PI flow apoptosis detection kit to detect the influence of DFMO on proliferation and apoptosis of the breast cancer tamoxifen-resistant cells by single use or combined use of tamoxifen. The apoptosis test results are shown in fig. 4, and the results show that: the DFMO can obviously promote the apoptosis of MCF-7 tamoxifen resistant cells MCF-7 by single treatment, and shows stronger apoptosis induction effect on tamoxifen resistant breast cancer cells after combined treatment of tamoxifen.
The above embodiments are preferred embodiments of the present invention, and besides, the present invention may be implemented in other ways, and any obvious substitution is within the scope of the present invention without departing from the concept of the present invention.
Claims (10)
- Use of odc1 as a marker for the preparation of a reagent for diagnosing breast cancer tamoxifen resistance.
- Application of ODC1 inhibitor in preparing medicine for treating breast cancer.
- 3. The use according to claim 2, characterized in that: the ODC1 inhibitor is DFMO.
- 4. The use according to claim 2, characterized in that: the breast cancer is ER alpha positive breast cancer.
- Use of an odc1 inhibitor for the manufacture of a medicament for improving the resistance of a patient to breast cancer.
- 6. The use according to claim 5, characterized in that: the ODC1 inhibitor is DFMO.
- 7. The use according to claim 5, characterized in that: the breast cancer drug resistance refers to breast cancer tamoxifen drug resistance.
- Application of ODC1 inhibitor and tamoxifen in preparing medicines for breast cancer.
- 9. The use according to claim 8, characterized in that: the ODC1 inhibitor is DFMO.
- 10. The use according to claim 8, characterized in that: the breast cancer is ER alpha positive breast cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311759824.2A CN117701715A (en) | 2023-12-20 | 2023-12-20 | Application of ODC1 and inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311759824.2A CN117701715A (en) | 2023-12-20 | 2023-12-20 | Application of ODC1 and inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117701715A true CN117701715A (en) | 2024-03-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311759824.2A Pending CN117701715A (en) | 2023-12-20 | 2023-12-20 | Application of ODC1 and inhibitor thereof in diagnosis and treatment of drug resistance of breast cancer tamoxifen |
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| Country | Link |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998014188A1 (en) * | 1996-10-04 | 1998-04-09 | Ilex Oncology, Inc. | Dfmo and taxol for the treatment or prevention of breast cancer |
| CN101217956A (en) * | 2005-05-05 | 2008-07-09 | 康宾纳特克斯公司 | Compositions and methods for treatment for neoplasms |
| US20230123908A1 (en) * | 2006-05-18 | 2023-04-20 | Caris Mpi, Inc. | Molecular profiling of tumors |
-
2023
- 2023-12-20 CN CN202311759824.2A patent/CN117701715A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998014188A1 (en) * | 1996-10-04 | 1998-04-09 | Ilex Oncology, Inc. | Dfmo and taxol for the treatment or prevention of breast cancer |
| CN101217956A (en) * | 2005-05-05 | 2008-07-09 | 康宾纳特克斯公司 | Compositions and methods for treatment for neoplasms |
| US20230123908A1 (en) * | 2006-05-18 | 2023-04-20 | Caris Mpi, Inc. | Molecular profiling of tumors |
Non-Patent Citations (3)
| Title |
|---|
| THRESIA THOMAS等: "ADDITIVE GROWTH-INHIBITORY EFFECTS OF DL-~-DIFLUOROMETHYLORNITHINE AND ANTIESTROGENS ON MCF-7 BREAST CANCER CELL LINE", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 148, no. 3, 13 November 1987 (1987-11-13), pages 1338 - 1345 * |
| 李金锋 等: "乳腺浸润癌癌前病变的研究现状", 国外医学.肿瘤学分册, vol. 29, no. 3, 30 June 2002 (2002-06-30), pages 213 - 216 * |
| 田富国: "乳腺癌非手术治疗", vol. 1, 30 April 2016, 华中科技大学出版社, pages: 190 - 192 * |
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