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View the Table of Contents for the January 15 issue of Cancer Research.
Page 820
Efuet et al. Page 1040
Farnesyl transferase and geranylgeranyl transferase inhibitors target constitutively active, mutated Ras by blocking post-translational prenylation. In series of studies using breast tumor models, Efuet et al. show that agents possessing an active lactone moiety (isoprenoid inhibitors and statins) mediate their cell cycle inhibitory activity by blocking the chymotrypsin activity of the proteasome in vitro. These findings provide evidence that the action of these inhibitors on tumor growth is not tightly linked to Ras, implicating other pathways such as the proteasome as an alternate mechanism. These results may lead to new therapeutic strategies in targeted treatment of breast and other types of Ras-dependent tumors.
Yoshimura et al. Page 1096
One of the most important sites of metastases for many cancers is the liver. By administering an engineered attenuated hepatotropic Listeria monocytogenes bacterium, vaccine-induced antitumor immune responses are selectively targeted to the liver, resulting in successful elimination of established hepatic metastases. These intrahepatic responses are mediated by a combination of microbe-induced innate and vaccine-induced CD8 T-cell responses. This work demonstrates that targeted microbes can be used to focus antitumor immunity to specific organs affected by metastases.
The mechanisms underlying tumor-specific T-cell anergy and induction of tolerance are not well known. The accumulation of myeloid suppressor cells (MSCs) correlates with immune dysfunction in tumor-bearing mice and cancer patients. Huang et al. identified a subpopulation of these suppressor cells, Gr-1+CD115 (M-CSF receptor)+F4/80+ MSCs, that induced the development of Foxp3+ T regulatory cells (Treg) both in vitro and in tumor-bearing mice. The induction of Treg by MSCs required IFN-γ and IL-10 but was independent of the nitric oxide-mediated suppressive mechanism. These findings demonstrate a novel in vivo immune suppressive mechanism by which MSCs can suppress antitumor responses.
Bettuzzi et al. Page 1234
In a pilot trial, green tea catechins (GTCs) were used for chemoprevention of human prostate cancer. Efficacy was proven 90% in high-risk HG-PIN volunteers. Also, benign prostate hyperplasia symptoms were reduced, as secondary observation. This is the first study showing that GTCs have potent in vivo chemoprevention activity in humans. Thus, GTC administration is a safe and effective therapy for treating premalignant lesions, filling a therapeutic void before prostate cancer develops. If confirmed, these finding anticipate novel chemotherapeutic strategies in which GTC administration may greatly reduce the incidence of prostate cancer with a tremendous social and clinical impact in Western countries.