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.

Our method (parts I−VII) for estimating solvent shifts of species that have strong specific interactions (e.g., hydrogen bonding) with the solvent is applied to calculate the absorption and fluorescence solvatochromic (solvent) shifts of dilute pyridazine in water. The interpretation of the spectroscopy of pyridazine is complicated by the possibility that the S1 state is nearly degenerate with one or more other electronic states. We evaluate solvent shifts for all possible low-lying states and conclude that if near degeneracies do indeed occur, then considerable, nonobserved changes in the absorption band shape would be expected with solvent variation. This lends strong support to the arguments suggesting that S2 is somewhat removed from S1. Only orthodox linear hydrogen bonding to the ground state is found to be consistent with observed solvent shifts; hydrogen bonding to the excited states of pyridazine is shown to be relatively weak, and the generally accepted interpretations of the solvent shifts of pyridazine are explicitly verified from a molecular point of view. This completes our detailed molecular analysis of the solvent shifts of the diazines in dilute solution.

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.

A model is developed for the solvent shift of the center of an electronic absorption or emission band and is applied to the interpretation of the spectra of dilute pyrimidine in water. It is based on the use of standard simulation techniques such as molecular dynamics and Monte Carlo to calculate the liquid structure around the chromophore in its initial electronic state; the solvent shift is then deduced by considering the changes in the electrostatic distribution of the chromophore on vertical Franck–Condon excitation. During the solvent-shift evaluation only, spherical boundary conditions are used and the sample, containing both the solute and a large number of explicitly polarizable solvent molecules, is placed inside a dielectric continuum. The results show that the solvent shifts of both the absorption and fluorescence spectra of pyrimidine in water are comprised of approximately equal contributions from specific hydrogen-bonding interactions and long-range–plus–nonspecific dipole solvation effects. The solvent shift is shown to be very sensitive to the structure of the liquid. A specific aim of our approach is to develop a method applicable to molecular electronic devices, and to inorganic complexes.

AIMTo compare the expression levels of interleukin (IL)-6 in colorectal cancer (CRC) tissues and adjacent non-cancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC.METHODSFifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTSIL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues (P < 0.001). IL-6 expression was positively correlated with tumour TNM stage (P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC (P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC.CONCLUSIONIL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.