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Immunomodulatory drugs such as lenalidomide (LEN) have shown significant anti-tumor activity against hematologic malignancies and they may have similar actions on solid tumors as well. We studied the effect of a new analog of the immunomodulatory drugs (CC-122) on the growth of hepatocellular carcinoma (HCC) and explored mechanisms of anti-tumor activity by analyzing expression of a novel oncogenic T-cell factor (TCF)-4 J and its downstream gene activation. LEN and CC-122 significantly reduced the expression levels of TCF-4 J and its target genes (SPP1, AXIN2, MMP7, ASPH, CD24, ANXA1, and CAMK2N1); however, CC-122 was more potent. In a xenograft tumor model with a HAK-1A-TCF-4 J derived stable cells, tumor growth was significantly inhibited by CC-122, but not by LEN or vehicle control. The mice with HCC xenograft tumors treated with CC-122 exhibited decreased TCF-4 J expression compared to LEN and control. Furthermore, expression of TCF-4 J-responsive target genes (SPP1, AXIN2, MMP7, ASPH, JAG1, CD24, ANXA1, and CAMK2N1) was reduced by CC-122 and not by LEN or control. These results suggest that CC-122 inhibits HCC tumor growth through downregulation of the oncogenic TCF-4 J isoform.
This article was published in the following journal.
Name: Translational oncology
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A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
A rare tumor of the female genital tract, most often the ovary, formerly considered to be derived from mesonephric rests. Two varieties are recognized: (1) clear cell carcinoma, so called because of its histologic resemblance to renal cell carcinoma, and now considered to be of muellerian duct derivation and (2) an embryonal tumor (called also ENDODERMAL SINUS TUMOR and yolk sac tumor), occurring chiefly in children. The latter variety may also arise in the testis. (Dorland, 27th ed)
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
The founding member of the EPH FAMILY RECEPTORS. It was first cloned from an erythropoietin-producing human hepatocellular carcinoma cell line and is highly conserved among many mammalian species. Overproduction of the EphA1 receptor is associated with tumors and tumor cells of epithelial origin. It is also expressed at high levels in LIVER; LUNG; and KIDNEY; which is in contrast to many other members of the Eph receptor that are found primarily in tissues of the nervous system.
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...