786-O Xenograft Model - Altogen Labs (2024)

786-O Xenograft Model - Altogen Labs (1)

786-O xenograft model

The most common type of kidney cancer is renal cell carcinoma (RCC), accounting for nearly 3 percent of tumors in adults. The exact cause of renal cell carcinoma is currently unknown. Xenograft rodent models are essential in preclinical studies for testing novel therapeutic modalities to address renal cancer. The 786-O epithelial cell line is isolated from primary adenocarcinoma cells of the kidney tissue of a 58-year-old Caucasian male patient with renal cell adenocarcinoma. 786-O is a hypertriploid cell line that produces parathyroid hormone (PTH) and is tumorigenic in nude mice. 786-O cells display both microvilli and desmosomes. The 786-O cell line is invaluable for studying human infections related to the prostate. 786-O is one of the first RCC cell lines that is commonly used in RCC-focused research. A 2013 renal xenograft study published in British Journal of Cancer, demonstrates that resistance to sunitinib is accompanied by increased COX-2 expression in areas of tumor hypoxia in the 786-O xenograft model. Also, the COX-2 inhibitor celecoxib enhances the effectiveness of sunitinib in the 786-O xenograft model by delaying time to progression if administered early in the course of sunitinib therapy. Celecoxib showed activity in the 786-O tumor model as a single agent and in combination with sunitinib. The 786-O RCC line expresses high levels of VEGF (Vascular endothelial growth factor), which stimulates angiogenesis and gives rise to tumors in nude mice. A 2010 study (Bhatt et al.) used the 786-O model to study the mechanism of resistance that often surfaces within 6-12 months of anti-angiogenesis treatment of metastatic renal cancer. Their results demonstrated that treatment with either sunitinib or sorafenib initially targeted VEGF however resistance was in part due to resumption of angiogenesis correlated to downregulation of IFN-gamma angiostatic chemokines; when the conventional chemotherapies were combined with CXCL9 (one of the angiostatic chemokines) treatment, prolonged reduction of angiogenesis was observed thus providing potential combination clinical strategies for overcoming resistance. Lastly, a 2017 Tumor Biology study used the 786-O model to demonstrate that Rap2B can promote angiogenesis through PI3K/AKT pathway in vivo, and loss of Rap2B could be a novel strategy for RCC anti-angiogenesis therapy. The 786-O cell line (human kidney) is used to create the CDX (Cell Line Derived Xenograft) 786-O xenograft mouse model that allows researchers to study COX-2 inhibitors and anti-angiogenesis therapy as well as anti-cancer agents targeting RCC cells.

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Basic study design

1. 786-O cells are cultured under aseptic conditions in exponential growth phase prior to injection.
2. The cells are trypsinized from the flasks and viable cell counts are determined using a trypan blue exclusion assay (98% cell viability required). The cell suspension is adjusted to the appropriate density.
3. Each mouse (athymic BALB/C or NOD/SCID, 10-12 w.o.) receive a subcutaneous injection in the flank of the hind leg of one million cells in a volume of 100 microliters of Matrigel 786-O cell suspension.
4. The injection sites are manually palpated three times weekly until tumors are established. Tumors are measured using digital calipers until they reach an average size of 50-150 mm3.
5. Animals are randomized into treatment cohorts and administration of the compound of interest is performed according to the treatment schedule.
6. Tumors are measured daily and mouse weights recorded 3 times weekly.
7. Animals are euthanized when tumor size reaches 2,000 sq. millimeters or the IACUC protocol predetermined size limit.
8. Necropsy and tissue collections are performed as defined for termination of experiment.
9. Tumors are excised, weighed and documented by digital imaging.
10. Standard gross necropsies are performed and tissues are collected for downstream analysis.
11. Tumors and tissues aresnap frozen in LN2 and prepared for histology or gene expression analysis.

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Animal handling and maintenance at the Altogen Labs facility is IACUC-regulated and GLP-compliant. Following acclimation to the vivarium environment, mice are sorted according to body mass. The animals are examined daily for tumor appearance and clinical signs. We provide detailed experimental procedures, health reports and data (all-inclusive report is provided to the client that includes methods, results, discussion and raw data along with statistical analysis). Additional services available include collection of tissue, histology, isolation of total protein or RNA and analysis of gene expression.

Following options are available for the 786-O xenograft model:

  • 786-O Tumor Growth Delay (TGD; latency)
  • 786-O Tumor Growth Inhibition (TGI)
  • Dosing frequency and duration of dose administration
  • 786-O tumor immunohistochemistry
  • Blood chemistry analysis
  • Toxicity and survival (optional: performing a broad health observation program)
  • Gross necropsies and histopathology
  • Lipid distribution and metabolic assays
  • Imaging studies

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786-O Xenograft Model - Altogen Labs (2024)

FAQs

What is the xenograft model of cancer? ›

Xenograft models are based on the implantation of human tumor cells into immunocompromised mice to avoid graft versus host reaction of the mouse against the human tumor tissue. Reaction Biology's in vivo tumor models are derived from a variety of origins such as breast, colon, lung, skin, blood.

What is the xenograft model of breast cancer? ›

Breast cancer xenograft models are used to study the biology of breast cancer, including the mechanisms of tumor growth and metastasis, as well as the tumor's response to various treatments types.

What is a subcutaneous xenograft model? ›

Orthotopic xenografts are defined as the implantation of cancer cells into the same organ or tissue from which the cancer originated in the human, while subcutaneous xenografts are the implantation of cancer cells under the skin of an immunodeficient mouse or SRG rat.

What is CDX xenograft? ›

Patient-derived xenograft (PDX): PDX models use tumor tissue surgically removed from a cancer patient. • Cell line-derived xenograft (CDX): Commercially available cancer cell lines, PDX-derived cell lines or any other immortalized cell line can also be implanted into immunodeficient mice to support any tumor study.

What are the disadvantages of Xenograft? ›

One major disadvantage of subcutaneous xenograft tumor models is that the microenvironment of the implanted tumor does not reproduce the environment in which the tumor grows [47][48][49].

What are the risks of Xenograft? ›

Xenotransplantation may transmit microorganisms (including currently unknown or unrecognized ones) from animal tissue or organs to transplant recipients 〚3〛, 〚4〛, 〚5〛, 〚6〛, 〚7〛, 〚8〛, 〚9〛. Such infections could potentially be transmitted from person to person, putting the general population at risk as well.

What are the advantages of the xenograft model? ›

Xenografts share many of the advantages of allografts, but debate exists concerning their efficacy compared with allografts. Compared with allografts, xenografts are reported to have increased connective tissue ingrowth, delayed vascularization, and slower rates of resorption.

What is the success rate of xenograft? ›

Results. Tumor xenograft models were generated from 67 patients; 30 (44.8%) were successful and 37 (55.2%) failed. Xenograft models could recapitulate the pathology and genetic information of the primary tumors.

Why is xenograft important? ›

The term xenograft refers to a tissue or organ that is derived from a species that is different from the recipient of the specimen. They are powerful research tools in oncology as well as essential for treating wounds in the clinic.

What is another word for Xenograft? ›

Definitions of xenograft. noun. tissue from an animal of one species used as a temporary graft (as in cases of severe burns) on an individual of another species. synonyms: heterograft.

What do you mean by xenograft? ›

(ZEE-noh-graft) The transplant of an organ, tissue, or cells to an individual of another species.

What is an example of a xenograft? ›

Xenografts are grafts taken from a donor of another species. Currently, anorganic, bovine-derived, equine-derived bones, and coral skeleton have been marketed for periodontal regenerative and implant therapy.

What is a xenograft model? ›

Xenograft models are animal models that are generated by the implantation of tumor cell lines (cell line-derived xenograft) or direct transplantation of patient tumor cells (patient-derived xenograft) into an immunodeficient animal.

What is a CDX in oncology? ›

Companion diagnostics (CDx) provides information essential for the safe and effective use of a corresponding intervention. Clinical practice is shifting to the era of precision medicine, and CDx is increasingly used to identify eligible patients for targeted treatments.

Is a xenograft permanent? ›

Allograft and xenograft skin grafts are usually temporary. They cover the damaged skin until the wound heals or the person grows enough healthy skin to use for a permanent skin graft.

What is allograft vs xenograft model? ›

2.1 Xenograft models of prostate cancer. A xenograft is an inoculation of a tumor cell suspension or implantation of tissue pieces from a foreign species, in contrast to an allograft, in which the transplantable material is from the same species.

What is an example of a Xenograft? ›

Xenografts are grafts taken from a donor of another species. Currently, anorganic, bovine-derived, equine-derived bones, and coral skeleton have been marketed for periodontal regenerative and implant therapy.

What is the principle of Xenograft? ›

Orthotopic xenograft models involve implanting tumors into defined sites within the animal to mimic metastases to specific organs. This concept is based on the premise that tumor metastases are not random, but occur because of a specific tropism or affinity of various tumors to grow in specific sites (54).

What is the purpose of a Xenograft? ›

Cancer drugs and other types of treatment may be tested on xenografts to see how well they work before they are given to the patient. Patient-derived xenografts may be used to help plan treatment and learn what the best treatment may be for a patient. They are also being used in the development of new cancer drugs.

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