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Novel target PCDHB2 for breast cancer osseous metastasis diagnosis and treatment

A PCDHB2, breast cancer technology, applied in the field of biomedicine, can solve the problems of lack of breast cancer bone metastasis, difficult clinical treatment, and inability to significantly improve the survival expectation of patients, and achieve the effect of inhibiting anti-anoikis and inhibiting bone metastasis.

Active Publication Date: 2019-09-10
江门市中心医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current treatment for bone metastasis of breast cancer is palliative. Whether it is surgery, radiotherapy or drug treatment, it only relieves and improves the corresponding symptoms, and cannot significantly improve the patient's survival expectancy
Once bone metastasis occurs, it not only seriously affects the quality of life and life expectancy of patients, but also brings great difficulties to clinical treatment.
[0003] In recent years, research on molecular markers for the diagnosis and prognosis of breast cancer bone metastasis has made great progress, but there is still a lack of clinically specific molecular markers that can effectively predict bone metastasis of breast cancer and serve as therapeutic targets

Method used

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  • Novel target PCDHB2 for breast cancer osseous metastasis diagnosis and treatment
  • Novel target PCDHB2 for breast cancer osseous metastasis diagnosis and treatment
  • Novel target PCDHB2 for breast cancer osseous metastasis diagnosis and treatment

Examples

Experimental program
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Embodiment approach

[0049] As an embodiment, the reagent for quantifying the level of PCDHB2 mRNA is selected from primers, probes, and gene chips.

[0050] As an embodiment, the reagent for quantifying PCDHB2 protein level is selected from antibodies and protein chips.

[0051] The inventors have determined that down-regulating or inhibiting the expression of Protocadherin Beta 2 (PCDHB2) can significantly inhibit the bone metastasis of breast cancer cells in mice and inhibit the resistance of breast cancer cells to anoikis through animal in vivo and cell in vitro experiments. Apoptosis, as well as migration and invasion abilities; the above undoubtedly confirm that PCDHB2 can be specifically used as a therapeutic target for bone metastasis of breast cancer.

[0052] In the third aspect, the present invention proposes the use of PCDHB2 inhibitory reagents in the preparation of drugs for preventing, inhibiting and / or treating bone metastasis of breast cancer.

[0053] The PCDHB2 inhibitory agent...

Embodiment 1

[0059] Example 1, PCDHB2 is highly expressed in breast cancer tissue with bone metastasis

[0060] Transcript sequencing was performed on 29 collected breast cancer tissues, including 12 LumB breast cancer tissues with the same clinicopathological stage (4 cases with bone metastasis within 7 years; 8 cases without bone metastasis within 7 years), 9 The tissues of Her2 type breast cancer (3 cases with bone metastasis within 7 years; 6 cases without bone metastasis within 7 years) and 8 cases of BasL type breast cancer tissues (3 cases with bone metastasis within 7 years; 5 cases without bone metastasis within 7 years), compared Differentially expressed genes between breast cancer tissues with bone metastasis within 7 years and breast cancer tissues without bone metastasis within 7 years, found that 62 genes were up-regulated and 353 genes were down-regulated in breast cancer tissues with bone metastasis within 7 years, of which Such as figure 1 As shown, PCDHB2 was significant...

Embodiment 2

[0062] Example 2. PCDHB2 is specifically highly expressed in BasL breast cancer, and it indicates an earlier risk of bone metastasis

[0063] 472 breast cancer tissues of all types were collected, including 125 cases of LumA type, 140 cases of LumB type, 47 cases of Her2 type, 160 cases of BasL type, and 52 cases of benign breast hyperplasia for immunohistochemical analysis. The method is as follows:

[0064] After heat-treating tissue sections at 65°C for 1 hour, dewax in xylene twice for 5 minutes each time; hydrate the sections with 100% ethanol, 95% ethanol, 85% ethanol, 75% ethanol and pure water successively, 1 minute each time; After taking it out, add 3% hydrogen peroxide dropwise and incubate at room temperature for 10 minutes to inactivate endogenous peroxidase; place the slice in a container filled with EDTA pH9.0 repair solution, and repair it under high pressure in a pressure cooker for 10 minutes; Surround the tissue with a pen and rinse it with PBS buffer for 3 ...

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Abstract

The invention discloses a novel target PCDHB2 for breast cancer osseous metastasis diagnosis and treatment. The significantly high expression of the PCDHB2 in multiple subtype breast cancer tissue with the osseous metastasis is determined, the high expression of the PCDHB2 in all kinds of breast cancer tissue, BasL breast cancer tissue and other types (LumA type, Lumb type and Her2 type) of breastcancer tissue indicates the occurrence of earlier osseous metastasis, the PCDHB2 is not associated with distant metastasis of other parts of the breast cancer (brain, lung and liver), and it is suggested that the PCDHB2 can more specifically predict the occurrence of the breast cancer osseous metastasis. The down-regulation of PCDHB2 expression can significantly inhibit osseous metastasis of breast cancer cells and inhibit anoikis, migration and invasion resisting capacities of the breast cancer cells, and the PCDHB2 is the novel target of diagnosis, prognosis and treatment of breast cancer osseous metastasis.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically relates to a new target PCDHB2 for the diagnosis and treatment of breast cancer bone metastasis. Background technique [0002] With the change of nutritional structure and the trend of aging, the incidence of breast cancer has a significant increase trend. About 70% of breast cancer patients die with at least one bone metastases; patients with breast cancer who have bone metastases even before the onset of clinical symptoms, or who do not develop bone metastases after in situ breast cancer treatment, However, bone metastases appear after several years or even more than ten years, which brings great difficulties to clinical treatment. Bone-related complications, such as pain, hypercalcemia, pathological fractures, spinal cord or nerve root compression, etc., are accompanied by bone metastasis of tumors, which seriously affect the quality of life and survival time of patients. The...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886G01N33/574A61K45/00A61P35/04
CPCA61K45/00A61P35/04C12Q1/6886C12Q2600/118C12Q2600/158G01N33/57415G01N33/57484
Inventor 任栋李宇明杨春潇张鑫王斌
Owner 江门市中心医院
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