<meta charset="utf8"></head><body>骨肉瘤 PDX 小鼠模型的方案：研究生长和耐药性

<ol>
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A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathways+of+immune+exclusion+in+metastatic+osteosarcoma+are+associated+with+inferior+patient+outcomes.">Pathways of immune exclusion in metastatic osteosarcoma are associated with inferior patient outcomes.</a> J Immunother Cancer. 9 (5), e001772 (2021).</li><li>Miwa, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+and+emerging+targets+in+immunotherapy+for+osteosarcoma.">Current and emerging targets in immunotherapy for osteosarcoma.</a> J Oncol. 2019, 7035045 (2019).</li><li>Eaton, B. 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J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-derived+tumor+xenografts+as+models+for+oncology+drug+development.">Patient-derived tumor xenografts as models for oncology drug development.</a> Nat Rev Clin Oncol. 9 (6), 338-350 (2012).</li><li>Yoshida, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+patient-derived+tumor+xenograft+models+and+tumor+organoids.">Applications of patient-derived tumor xenograft models and tumor organoids.</a> J Hematol Oncol. 13 (1), 4 (2020).</li><li>Stitzlein, R. N., Wojcik, J., Sebro, R. A., Balamuth, N. J., Weber, K. 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S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+practical+protocol+to+prepare+paraffin-embedded+whole+tick+histology+sections.">A practical protocol to prepare paraffin-embedded whole tick histology sections.</a> Ticks Tick Borne Dis. 14 (4), 102162 (2023).</li><li>Chang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Matrine+inhibits+prostate+cancer+via+activation+of+the+unfolded+protein+response/endoplasmic+reticulum+stress+signaling+and+reversal+of+epithelial+to+mesenchymal+transition.">Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition.</a> Mol Med Rep. 18 (1), 945-957 (2018).</li><li>de Alava, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ewing+sarcoma,+an+update+on+molecular+pathology+with+therapeutic+implications.">Ewing sarcoma, an update on molecular pathology with therapeutic implications.</a> Surg Pathol Clin. 10 (3), 575-585 (2017).</li><li>Hidalgo, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-derived+xenograft+models:+An+emerging+platform+for+translational+cancer+research.">Patient-derived xenograft models: An emerging platform for translational cancer research.</a> Cancer Discov. 4 (9), 998-1013 (2014).</li><li>Eoh, K. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+clinical+features+and+outcomes+in+epithelial+ovarian+cancer+according+to+tumorigenicity+in+patient-derived+xenograft+models.">Comparison of clinical features and outcomes in epithelial ovarian cancer according to tumorigenicity in patient-derived xenograft models.</a> Cancer Res Treat. 50 (3), 956-963 (2018).</li><li>Stewart, E. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+utility+of+patient-derived+xenografts+to+determine+biomarkers+of+prognosis+and+map+resistance+pathways+in+EGFR-mutant+lung+adenocarcinoma.">Clinical utility of patient-derived xenografts to determine biomarkers of prognosis and map resistance pathways in EGFR-mutant lung adenocarcinoma.</a> J Clin Oncol. 33 (22), 2472-2480 (2015).</li><li>Kresse, S. H., Meza-Zepeda, L. A., Machado, I., Llombart-Bosch, A., Myklebost, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preclinical+xenograft+models+of+human+sarcoma+show+nonrandom+loss+of+aberrations.">Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations.</a> Cancer. 118 (2), 558-570 (2012).</li><li>Dobrolecki, L. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-derived+xenograft+(PDX)+models+in+basic+and+translational+breast+cancer+research.">Patient-derived xenograft (PDX) models in basic and translational breast cancer research.</a> Cancer Metastasis Rev. 35 (4), 547-573 (2016).</li><li>Abdolahi, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-derived+xenograft+(PDX)+models,+applications+and+challenges+in+cancer+research.">Patient-derived xenograft (PDX) models, applications and challenges in cancer research.</a> J Transl Med. 20 (1), 206 (2022).</li><li>Deng, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+whole-genome+sequencing+identifies+recurrent+genomic+alterations+in+commonly+used+breast+cancer+cell+lines+and+patient-derived+xenograft+models.">Deep whole-genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models.</a> Breast Cancer Res. 24 (1), 63 (2022).</li><li>Chen, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Generation+and+characterization+of+patient-derived+xenografts+from+patients+with+osteosarcoma.">Generation and characterization of patient-derived xenografts from patients with osteosarcoma.</a> Tissue Cell. 79, 101911 (2022).</li><li>Fortuna-Costa, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+association+between+successful+engraftment+of+osteosarcoma+patient-derived+xenografts+and+clinicopathological+findings.">An association between successful engraftment of osteosarcoma patient-derived xenografts and clinicopathological findings.</a> Histol Histopathol. 35 (11), 1295-1307 (2020).</li><li>Beck, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Canine+and+murine+models+of+osteosarcoma.">Canine and murine models of osteosarcoma.</a> Vet Pathol. 59 (3), 399-414 (2022).</li></ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>10% formalin neutral solution</td>
			<td>Wuhan Saiweier Biotechnology Co., Ltd</td>
			<td>G1101-500ml</td>
			<td>Fix the tissues</td>
		</tr>
		<tr>
			<td>Autoclave</td>
			<td>Japan Hiryama Company</td>
			<td>HVE-50</td>
			<td>Sterilization surgical instruments</td>
		</tr>
		<tr>
			<td>CAnN.Cg-Foxn1nu/Crl</td>
			<td>Shanghai SLAC Laboratory Animal Co, Ltd.</td>
			<td>/</td>
			<td>Animal</td>
		</tr>
		<tr>
			<td>Caliper</td>
			<td>Yantai Green Forest Tools Co., Ltd.</td>
			<td>034180A</td>
			<td>Measure the tumor volume</td>
		</tr>
		<tr>
			<td>Dish (60mm)</td>
			<td>Shanghai NianYue Biotechnology Co., Ltd</td>
			<td>430166, Corning</td>
			<td>Sample placment during transplantation</td>
		</tr>
		<tr>
			<td>Disinfectant cotton balls</td>
			<td>Shanghai Honglong Industrial Co., Ltd.</td>
			<td>20230627</td>
			<td>Disinfect the skin of mice</td>
		</tr>
		<tr>
			<td>Disposable sterile gloves</td>
			<td>Guilin Hengbao Health Protection Co., Ltd.</td>
			<td>YT21131</td>
			<td>Sterile operation</td>
		</tr>
		<tr>
			<td>Double lion Irradiated Rodent Diet</td>
			<td>Suzhou Shuangshi Experimental Animal Feed Technology Co., Ltd.</td>
			<td>GB 14924.3</td>
			<td>Animal feed</td>
		</tr>
		<tr>
			<td>Electronic scale</td>
			<td>Shanghai NianYue Biotechnology Co., Ltd</td>
			<td>1-2000</td>
			<td>Weigh the weight of the tumor</td>
		</tr>
		<tr>
			<td>Eosin</td>
			<td>Shanghai Gengyun Biotechnology Co., Ltd</td>
			<td>E4009-25G</td>
			<td>Hematoxylin eosin stain</td>
		</tr>
		<tr>
			<td>Hematoxylin</td>
			<td>Shanghai Gengyun Biotechnology Co., Ltd</td>
			<td>H3136-25G</td>
			<td>Hematoxylin eosin stain</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>Shenzhen RWD Life Technology Co., Ltd</td>
			<td>VETEASY</td>
			<td>Mouse anesthesia&#160;</td>
		</tr>
		<tr>
			<td>IVCs mice cage</td>
			<td>Suzhou Monkey King Animal Experimental Equipment Technology Co., Ltd.</td>
			<td>HH-MMB-2</td>
			<td>Animal barrier</td>
		</tr>
		<tr>
			<td>Mark pen</td>
			<td>Zebra Trading (Shenzhen) Co., Ltd.</td>
			<td>YYST5</td>
			<td>Mark the surgical incision</td>
		</tr>
		<tr>
			<td>Olympus Optical microscope</td>
			<td>Japanese Olympus Company</td>
			<td>BH20</td>
			<td>Scan tissue slices</td>
		</tr>
		<tr>
			<td>Ophthalmic ointment</td>
			<td>Shanghai Gengyun Biotechnology Co., Ltd</td>
			<td>SOICOEYEGRL</td>
			<td>Avoid dry eyes of mice during anesthesia</td>
		</tr>
		<tr>
			<td>Ophthalmic scissors</td>
			<td>Shanghai NianYue Biotechnology Co., Ltd</td>
			<td>Y00030 JZ</td>
			<td>Cut the skin</td>
		</tr>
		<tr>
			<td>Ophthalmic tweezers</td>
			<td>Shanghai NianYue Biotechnology Co., Ltd</td>
			<td>BS-ZER-S-100 Biosharp</td>
			<td>Hold osteosarcoma tissues during transplantation</td>
		</tr>
		<tr>
			<td>Paraffin</td>
			<td>Jiangsu Shitai Experimental Equipment Co., Ltd.</td>
			<td>80200-0015</td>
			<td>Buried osteosarcoma tissue</td>
		</tr>
		<tr>
			<td>Paraffin slicing machine</td>
			<td>Lyca Microsystem (Shanghai) Trading Co., Ltd.</td>
			<td>RM2235</td>
			<td>Osteosarcoma tissue section</td>
		</tr>
		<tr>
			<td>physiological saline</td>
			<td>Guangzhou Jinsheng Biotechnology Co., Ltd.</td>
			<td>605-004057</td>
			<td>Rinse and temporary storage of osteosarcoma tissue</td>
		</tr>
		<tr>
			<td>Scalpels</td>
			<td>Surgical Instrument Factory of Shanghai Medical Devices (Group) Co., Ltd.</td>
			<td>J11010-10# JZ</td>
			<td>Separation of osteosarcoma tissue and making surgical incisions</td>
		</tr>
		<tr>
			<td>Sterile hood</td>
			<td>Thermo Fisher Technology (China) Co., Ltd.</td>
			<td>ECO0.9</td>
			<td>Surgical operation table</td>
		</tr>
		<tr>
			<td>sterile surgical drapes</td>
			<td>Henan Huayu Medical Equipment Co., Ltd.</td>
			<td>20160090</td>
			<td>Provide sterile surgery area</td>
		</tr>
		<tr>
			<td>Straight needle holder</td>
			<td>Shanghai Gengyun Biotechnology Co., Ltd</td>
			<td>J31050 JZ</td>
			<td>Suture the wound</td>
		</tr>
		<tr>
			<td>Suture line</td>
			<td>Shanghai Pudong Jinhuan Medical Products Co., Ltd</td>
			<td>F3124</td>
			<td>Suture the wound</td>
		</tr>
		<tr>
			<td>Suture needle</td>
			<td>Shanghai Pudong Jinhuan Medical Products Co., Ltd</td>
			<td>F3124</td>
			<td>Suture the wound</td>
		</tr>
		<tr>
			<td>Tissue protective solution</td>
			<td>Nanjing Shenghang Biotechnology Co., LTD</td>
			<td>BC-CFM-03</td>
			<td>Maintain the activity of tissue cells</td>
		</tr>
		<tr>
			<td>Tube (50 mL)</td>
			<td>Shanghai Baisai, Biotechnology Co., Ltd.</td>
			<td>BLD-BL2002500</td>
			<td>Install formalin fixation solution</td>
		</tr>
	</tbody>
</table>

establishment of patient-derived xenograft mouse model with human osteosarcoma tissues

Osteosarcoma is a primary bone malignancy derived from interosseous lobe cells and is most common in adolescents as well as children. It often occurs in the epiphysis of the long diaphysis and is characterized by high malignancy, early metastasis, and poor prognosis1,2. Lung metastasis is the main cause of death in osteosarcoma patients. The 5-year survival rate of patients with non-metastatic osteosarcoma is 65%-70%3. However, over the last 40 years, the 5-year survival rate (only 20%) of patients with metastatic osteosarcoma has not significantly improved, and 25% of osteosarcoma patients have metastases at the time of diagnosis4. Currently, the first-line drugs for osteosarcoma treatment have reached a consensus, but there are still significant differences in chemotherapy regimen and treatment time5. It is important to perform preclinical experiments based on appropriate animal models to obtain more effective chemotherapy regimens.
Currently, models commonly used for osteosarcoma preclinical experiments include cell line-based in vitro cell culture and in vivo cell-derived xenografts (CDX), as well as patient-derived xenografts (PDX)6,7.
The cell lines are convenient for culturing and for use in in vitro studies, or for transplantation into immunodeficient mice to establish CDX models8. However, cell lines cultured in vitro may not accurately reflect the heterogeneity of malignancies and the individual characteristics of patients due to potential mutations that occur to adapt to the in vitro culture environment during repeated passages. Additionally, they lack the microenvironment and immune system necessary for tumor growth and development in vivo. While CDX models offer some advantages over in vitro cell culture, they still may not fully reflect the individual characteristics of osteosarcoma patients, although tumor tissues obtained from CDX models have limited intratumoral heterogeneity and immune system representation compared to cell lines cultured in vitro9. Therefore, establishing a preclinical model with high fidelity is crucial.
PDX models involve the immediate transplantation of freshly resected human cancer tissues into immunodeficient mice. This method allows for the faithful preservation of genetic, epigenetic, and heterogeneous characteristics of human malignancies for each patient, even after successive passages in mice. Furthermore, PDX models are known to accurately predict later clinical outcomes10, making them valuable tools for creating individualized treatments and advancing precision medicine research11.
This work describes the procedure for establishing a PDX model in immunodeficient mice by transplanting human osteosarcoma tissue. Such models serve as platforms for conducting preclinical experiments for osteosarcoma.

<meta charset="utf8"></head><body>作者聚焦：在免疫缺陷小鼠中复制人骨肉瘤进展用于癌症研究

人骨肉瘤组织患者来源的异种移植小鼠模型的建立

This study meticulously replicates the lateral progression of human osteosarcoma tissue growth in immunodeficient mice, providing a platform for studying the growth, the drug resistance, relapse, and metastasis of osteosarcoma. We realized the procedural steps involved in establishing a patient-derived xenograft model using human osteosarcoma tissue, thereby advising the preclinical research on osteosarcoma. This technical accuracy mimics the human cancer and maintains primary tumor similarity, facilitating the exploration of osteosarcoma biology and the treatment efficacy.

Watch this Scientific Journal Video about Author Spotlight: Replicating Human Osteosarcoma Progression in Immunodeficient Mice for Cancer Study at JoVE.com

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, ...

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Cancer Research

Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues

380 次观看.  Shanghai University of Traditional Chinese Medicine. 本研究精心复制了免疫缺陷小鼠人骨肉瘤组织生长的横向进展，为研究骨肉瘤的生长、耐药、复发和转移提供了一个平台。我们实现了使用人骨肉瘤组织建立患者来源的异种移植模型所涉及的程序步骤，从而为骨肉瘤的临床前研究提供建议。这种技术准确性模拟了人类癌症并保持原发肿瘤相似性，有助于探索骨肉瘤生物学和治疗效果。