Liposarcoma is a common subtype of soft tissue malignancies. Liposarcoma can be classified into atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myx/round cell liposarcoma, pleomorphic liposarcoma. Among them, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma are the more common subtypes in clinical practice, and dedifferentiated liposarcoma is more aggressive and Metastatic, and has a high recurrence rate; myxoid/round cell liposarcoma is second, has a higher risk of distant metastasis, and is more sensitive to radiotherapy and chemotherapy; pleomorphic liposarcoma is a less common clinical subtype, but its malignant The degree is high, the clinical efficacy is poor, and there is no ideal treatment plan at present. Therefore, in order to further accelerate the advancement of targeted therapy for liposarcoma, we provide endosome-targeted transfection of various related genes to study the molecular mechanism of liposarcoma.

Target Genes Delivered in vivo in Liposarcoma

Studies have found that many genes are related to the occurrence, development, metastasis and prognosis of liposarcoma, such as CDK4, MDM2, XPO1, OSBP and other genes. To advance the study of these related genes, we provide in vivo targeted transfection services for these genes.

Figure 1. The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma. (Zullow HJ, et al.; 2022)

CDK4

CDK4 amplification is found in most patients with retroperitoneal well-differentiated and dedifferentiated liposarcoma, and CDK4 is the most frequently amplified gene in liposarcoma. Through the phosphorylation of retinoblastoma (pRB), CDK4 can promote cell cycle progression to a certain extent, and promote the transition of cell division cycle initiation point from G1 to S phase. However, CDK4 inhibitors can inhibit the phosphorylation of downstream proteins of pRB, resulting in the disassembly of the pRB-related protein-E2F complex. Free E2F binds to DNA, and the positive regulation of cell cycle G1/S phase will also be inhibited by CDK4, which is beneficial to stagnate liposarcoma cells in G0/G1 phase, prevent cell proliferation, and achieve the purpose of treatment. Therefore, CDK4 is a good choice for the treatment of liposarcoma.

MDM2

The expression of MDM2 and p53 inhibit each other, and the balance of the two can maintain the normal differentiation of adipose tissue. When MDM2 is overexpressed, it inhibits the expression of p53 and promotes the continuous proliferation of adipocytes, leading to the occurrence of disease. Therefore, inhibiting the expression of MDM2 and activating the expression of p53 is an ideal solution for the treatment of well-differentiated and dedifferentiated liposarcoma.

XPO1

XPO1 can mediate the nuclear export of multiple tumor suppressor proteins, which can accumulate tumor suppressor proteins in the nucleus and mediate tumor cell apoptosis by binding to and inhibiting the nuclear export protein receptor. Since XPO1 inhibitors have little effect on normal cells while killing tumor cells, and have good safety, they are expected to become potential drug targets for liposarcoma.

OSBP

OSBP and related proteins (ORP) have the functions of regulating phospholipid and sterol metabolism and transport. Steroidal glycosides can inhibit the growth of highly malignant liposarcoma cells and have strong antitumor activity. Since steroidal glycosides can inhibit the formation of OSBP in adipocytes, it indicates that there is a certain relationship between the occurrence and development of liposarcoma cells and the expression of OSBP.

In addition to the above genes, there are interesting liposarcoma-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target liposarcoma tissue and be taken up by tumor cells to function in vivo. The system can help researchers overcome various challenges encountered during in vivo transfection:

• Relevant molecular function studies can only be carried out in vitro, lacking important in vivo data
• Using in vitro transfection system for in vivo transfection, the transfection efficiency is very low;
• The in vivo transfection system used is not specific to liposarcoma tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the liposarcoma tissue into the tumor tissue;
• The nucleic acid load of the in vivo transfection system is low, and it is difficult to achieve the expected effect;
• Etc…

Our Advantage:

• We can provide an in vivo transfection system for liposarcoma tissues and cells to achieve efficient transfection
• Our system can target multiple targets at the same time, improving targeting accuracy
• The in vivo transfection system has low toxicity to the body and is safe to use
• In vivo transfection system vectors can protect nucleic acids from degradation during in vivo delivery
• Persistent knockout effect in experimental animals after a single injection
• The system load is high, and the transfection needs of different doses can be completed
• Professional design and service team to provide you with reliable service and technical support
• Timely feedback of technical reports

CD BioSciences specializes in developing transfection systems and customizing transfection reagents for gene transfection using our core technologies. With our high-quality products and services, your transfection results can be greatly improved. If you can't find a perfect in vivo transfection system, you can contact us. We can provide one-to-one personal customization service.

References

1. GOUNDER M M, et al.; Phase IB study of selinexor, a first-in-class inhibitor of nuclear export, in patients with advanced refractory bone or soft tissue sarcoma. J Clin Oncol. 2016, 34(26): 3166-3174.
2. Nie L, Chen X, Gong J, Zhang M, Xu M, Chen N, Zhou Q (December 2020). Synchronous Renal Dedifferentiated Liposarcoma and Retroperitoneal Well-Differentiated Liposarcoma: A Case Report With Literature Review. International Journal of Surgical Pathology. 29 (6): 667–671.
3. Dei Tos AP (August 2000). Liposarcoma: new entities and evolving concepts. Ann Diagn Pathol. 4 (4): 252–66.
4. DICKSON M A, et al.; Progression-free survival among patients with well-differentiated or dedifferentiated liposarcoma treated with CDK4 inhibitor palbociclib: A phase 2 clinical trial. Jama Oncol. 2016, 2(7): 937-940.
5. Zullow HJ, et al.; The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma. Mol Cell. 2022, 82(9):1737-1750.e8.

* For research use only. Not for use in clinical diagnosis or treatment of humans or animals.