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Application of palbociclib in mucosal malignant melanoma

A malignant melanoma, mucosal technology, applied in the field of biomedicine, can solve the problems of limited promotion and application, and can not improve the five-year survival rate of patients.

Pending Publication Date: 2019-06-14
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

A number of clinical trials have shown that imatinib has drug resistance or relapse after treatment in the treatment of MM, which greatly limits its clinical promotion and application
In addition, the application of a variety of cytotoxic chemotherapy drugs, such as dacarbazine, cisplatin, paclitaxel, etc., did not improve the five-year survival rate of patients very well

Method used

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  • Application of palbociclib in mucosal malignant melanoma
  • Application of palbociclib in mucosal malignant melanoma
  • Application of palbociclib in mucosal malignant melanoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1 PDC (patient derived cell) screening sensitive candidate compounds

[0080] Inclusion criteria: Primary lesions of malignant melanoma occurring in the mucosa. There is no clear classification of mucosal malignant melanoma. Staging according to AJCC.

[0081] The obtained mucosal malignant melanoma samples were subjected to PDC model screening for sensitive inhibitors, as follows:

[0082] 1) Collect the PDC cells in the logarithmic growth phase, trypsinize, prepare the cell suspension, count the cells, and adjust the cell concentration to 2×10 4 a / ml;

[0083] 2) Inoculate the cells into a 96-well plate, 100ul of cell suspension per well, and set at least 3 auxiliary wells for each drug concentration;

[0084] 3) Place the cells in a 37°C, 5% carbon dioxide incubator and culture overnight;

[0085] 4) The next day after cell inoculation, according to the drug concentration gradient 0nM, 10 -3 nM, 10 -2 nM, 10 -1 nM, 1nM, 10nM, 100nM, 1000nM, 10uM, adde...

Embodiment 2

[0115] Example 2 Construction of xenograft tumor model and tumor suppressive effect of palbociclib

[0116] In order to better restore the biological and genetic characteristics of the patient's tissue-derived tumor, the samples collected in Example 1 were also used to construct a mouse xenograft tumor model, and the inhibitory effect of palbociclib was further verified.

[0117] 1) Put the sterile petri dish and surgical instrument package into the transfer bin for ultraviolet disinfection for 30 minutes;

[0118] 2) Weigh the mice, extract 10% chloral hydrate with a sterile syringe, calculate the dose according to the weight of the mice at 0.004ml / g, the maximum dose is not more than 0.1ml, and inject it into the abdominal cavity of the mice.

[0119] Precautions for anesthesia: Inject slowly, observe muscle tension at the same time, and the anesthesia is successful when the activity is obviously weakened or disappears;

[0120] After anesthesia, attention should be paid to...

Embodiment 3

[0129] Example 3 Whole Genome Sequencing

[0130] Whole-genome sequencing was performed on the five cell lines screened in Example 1, and it was found that in these mucosal malignant melanomas, CDK4, and well-known tumor driver genes such as TERT, MDM2, FRS2, KIT, BRAF, and CCND1 were significantly amplified.

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Abstract

The invention discloses an application of palbociclib in mucosal malignant melanoma. In particular, the present invention provides a therapeutic application of palbociclib known to treat ER+ / HER2-postmenopausal advanced breast cancer in mucosal malignant melanoma. Unlike common skin malignant melanoma, the palbociclib has the very good tumor inhibition effect on multi-source mucosal malignant melanoma with a very high degree of malignancy and no definitive treatment, which fills the blank of drug treatment for mucosal malignant melanoma and has great application prospects.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular, the invention relates to the application of palbociclib (Palbociclib) in the treatment of mucosal malignant melanoma. Background technique [0002] Malignant melanoma (Melanoma) is a tumor originating from melanocytes. Melanoma can be divided into skin, acral, mucous membrane and other melanomas with different genetic backgrounds. In European and American Caucasians, malignant melanoma is more common in the skin, and malignant melanoma of the fingertips and mucosa is relatively rare. Among them, malignant melanoma of the skin often occurs in the trunk, limbs, legs and other parts of chronic sun damage or non-chronic sun damage. It is a malignant tumor derived from normal melanocytes in the epidermis or original nevus cells. Serrated changes, not smooth and often rough with scaly or flaky desquamation. Sometimes there is exudate or blood, and the lesion may be higher than the skin surfa...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61P35/00A61K31/506
Inventor 孙树洋张志愿周榕韩永顾子悦杨桂柱
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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