Analysis of tissue samples from patients with HCC confirmed the observations made in the mouse model. mTORC2 and its signaling pathways, which promote de novo synthesis of fatty acids and lipids, are also activated in tumor samples from patients. Thus, the protein complex plays a critical role in the progression of benign "fatty liver" to aggressive HCC. The study provides important insights for the development of potential therapeutic interventions, as it shows that targeted lipogenesis inhibitors may have the potential to prevent tumor development.
The cap structure of eukaryotic mRNAs is bound by specific eIFs prior to association with the pre-initiation complex. Cap binding is accomplished by the initiation factor eIF-4F. This factor is actually a complex of 3 proteins; eIF-4E, A and G. The protein eIF-4E is a 24 kDa protein which physically recognizes and binds to the cap structure. eIF-4A is a 46 kDa protein which binds and hydrolyzes ATP and exhibits RNA helicase activity. Unwinding of mRNA secondary structure is necessary to allow access of the ribosomal subunits. eIF-4G aids in binding of the mRNA to the 43S pre-initiation complex.
The majority of patients who are going to ovulate will do so after the first course of therapy. If ovulation does not occur after three courses of therapy, further treatment with Clomid is not recommended and the patient should be reevaluated. If three ovulatory responses occur, but pregnancy has not been achieved, further treatment is not recommended. If menses does not occur after an ovulatory response, the patient should be reevaluated. Long-term cyclic therapy is not recommended beyond a total of about six cycles (see PRECAUTIONS ).