The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively upregulated in cancers. A novel class of anti-tropomyosin compounds has been developed that preferentially disrupts the actin cytoskeleton of tumor cells, impairing both tumor cell motility and viability. Our lead compound, TR100, is effective in vitro and in vivo in reducing tumor cell growth in neuroblastoma and melanoma models. Importantly, TR100 shows no adverse impact on cardiac structure and function, which is the major side effect of current anti-actin drugs. This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers. Cancer Res; 73(16); 5169-82. Ó2013 AACR.

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This work brings to a focus a series of papers concerning the modeling of solvent shifts in systems in which specific solute−solvent interactions such as hydrogen bonding occur:  we consider the interpretation of the metal-to-ligand charge-transfer (MLCT) absorption and electroabsorption spectra of Ru2+(NH3)5-pyrazine and its conjugate acid Ru2+(NH3)5-pyrazine-H+ in dilute aqueous solution. The electroabsorption spectra of these complexes (among the first to be observed for inorganic complexes) taken in S. G. Boxer's laboratory indicated that very small dipole moment changes occur on excitation from the ground to the excited state; it has been found necessary to develop and extensively test, in earlier parts of this series, a sophisticated model for solvent−solute interactions in order to interpret these experimental results. In our approach, first, ab initio MCSCF and INDO methods are used to estimate the gas-phase electronic excitation energies; second, Monte Carlo simulations are performed to determine the ground-state liquid structures; finally, the solvent shifts and excited-state dipole moments are evaluated on the basis of the gas-phase charge distributions and the explicit ground-state solvent structures. A variety of potential surfaces and boundary conditions are used in the simulations, and some variation in the liquid structures but little variation in the calculated solvent shifts and dipole moment changes result. The calculated solution frequencies agree quite well with those observed, and the anomalously low values observed for dipole moment change are reproduced; the Magnuson and Taube model for the electronic structure of Ru2+(NH3)5-pyrazine-H+ is verified.

Tumor progression can be affected by various cellular components of tumor cells and/or by tumor microenvironmental factors. The tumor microenvironment comprises a variety of nonmalignant stromal cells and inflammatory cytokines, which are pivotal in tumor promotion and progression. The transforming growth factor‑β (TGF‑β) ligands (TGF‑β1, 2 and 3) are secreted inflammatory cytokines, which are known to be involved in various aspects of tumor development through two transmembrane serine‑threonine kinase receptors, TGFβR1 and TGFβR2. TGF‑β promotes or inhibits tumorigenesis depending on the concurrent gene mutations and tissue microenvironment present through the small mothers against decapentaplegic (Smad) and non‑Smad pathways. This review aims to provide a comprehensive overview of the role of the TGF‑β pathway in tumor initiation and progression.

This study describes the epidemiology and clinical characteristics of patients hospitalized for ocular trauma in South-Central China. Notably, a high rate of firework-related ocular trauma occurred during the months adjacent to the Chinese New Year festival. Specific injury prevention strategies, such as the use of protective eyewear, need to target the workplace to reduce the incidence and severity of ocular trauma.