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Liver cancer is one of the most common malignant cancers worldwide. Systemic chemotherapy remains the major treatment option, but with severe adverse effects. Combinations of systemic with targeted treatments may provide effective therapeutics. The objectives of this study were to demonstrate if insulin-like growth factor-I receptor (IGF-IR) might serve as a functional target for liver cancer treatment and to investigate the chemo-sensitizing activity of IGF-IR downregulation. IGF-IR knockdown was achieved by stable transfection of liver cancer cells with IGF-IR small interfering RNA (siRNA). IGF-IR knockdown resulted in reduced growth, clonogenic survival, adhesion and migration of liver cancer cells, and increased sensitivities of liver cancer cells to apoptosis-inducing agents and chemotherapeutic drugs in vitro. In the animal studies, both IGF-IR knockdown and adriamycin (ADM) treatment significantly reduced the growth of liver tumors. IGF-IR knockdown enhanced the effect of ADM on tumor growth by further reducing tumor angiogenesis and inducing tumor cell apoptosis. The final tumor sizes in the IGFIR-siRNA, ADM-treated EGFP, and ADM-treated IGFIR-siRNA groups were significantly reduced by 52.5%, 33.8%, and 86.3%, respectively, compared with that in the EGFP control, suggesting that the ADM and the IGF-IR knockdown inhibit the growth of liver tumors in a synergistic manner. These results support that IGF-IR may serve as a functional molecular target for liver cancer treatment, and that the combination of systemic chemotherapy with targeted IGF-IR suppression may provide an effective treatment strategy for liver cancer.

We report on a family showing transmission of the fra(X) gene by 3 nonpenetrant, fra(X) negative, normally intelligent, full and half-brothers to their affected grandsons. The mothers of the affected boys are obligate carriers, fra(X) negative, and of normal intelligence. This family illustrates the “Sherman Paradox” and is compatible with the predictions of the Laird X-inactivation imprinting model. In addition molecular and/or cytogenetic studies have enabled at-risk relatives to learn more about their carrier fra(X) status and have allowed for more accurate genetic counselling. © 1992 Wiley-Liss, Inc.

1. At least two components of neuraminidase can be distinguished on the basis of thermolability and sedimentability by using the artificial fluorogenic substrate 4-methylumbelliferyl N-acetyl-alpha-D-neuraminate. 2. In crude homogenates, thermodenaturation at 25 degrees C showed a biphasic curve corresponding to component A (half-life, 21 min) and B (half-life, 85 min). The two components were partially resolved by centrifugation. A being soluble and B sedimentable. Both had similar pH-activity curves (pH optimum, 4.4), Km values (A, 0.10 mM; B, 0.06 mM) and molecular weight as determined by radiation inactivation (A, 67000; B, 63000). 3. The soluble A form was still aggregated or bound to membranous debris since almost all neuraminidase activity was eluted near or at the void volume of a Sephacryl S-300 column. 4. Both soluble and sedimentable fractions of placenta hydrolysed the GD1A ganglioside and N-acetyl-neuraminyl-D-lactose linearly for 12 h but no fetuin hydrolysis was detected. 5. The neuraminidase activity with the artificial fluorogenic substrate was inhibited by N-acetylneuraminyl-D-lactose but not by the GD1A ganglioside. These preliminary results suggest that there exist two closely related enzymes hydrolysing both the artificial substrate and N-acetylneuraminyl-D-lactose and a third one hydrolysing the GD1A ganglioside exclusively.