A potential therapeutic agent for human head and neck cancer (HNC), cetrimonium bromide (CTAB), was identified through a cell-based phenotype-driven high-throughput screen (HTS) of 2000 biologically active or clinically used compounds, followed by in vitro and in vivo characterization of its antitumor efficacy. The preliminary and secondary screens were performed on FaDu (hypopharyngeal squamous cancer) and GM05757 (primary normal fibroblasts), respectively. Potential hit compounds were further evaluated for their anticancer specificity and efficacy in combination with standard therapeutics on a panel of normal and cancer cell lines. Mechanism of action, in vivo antitumor efficacy, and potential lead compound optimizations were also investigated. In vitro, CTAB interacted additively with ␥ radiation and cisplatin, two standard HNC therapeutic agents.CTAB exhibited anticancer cytotoxicity against several HNC cell lines, with minimal effects on normal fibroblasts; a selectivity that exploits cancer-specific metabolic aberrations. The central mode of cytotoxicity was mitochondria-mediated apoptosis via inhibition of H ϩ -ATP synthase activity and mitochondrial membrane potential depolarization, which in turn was associated with reduced intracellular ATP levels, caspase activation, elevated sub-G 1 cell population, and chromatin condensation. In vivo, CTAB ablated tumor-forming capacity of FaDu cells and delayed growth of established tumors. Thus, using an HTS approach, CTAB was identified as a potential apoptogenic quaternary ammonium compound possessing in vitro and in vivo efficacy against HNC models.

Previous studies in other provinces of China (Beijing, Xinjiang, Shanxi, Jiangxi, Shanghai, Guangdong, and Taiwan) suggest that the distributions of lymphoma subtypes differ compared with Western populations. In order to evaluate the characteristics of malignant lymphoma in Sichuan, China, we analyzed case series data from incident lymphoma patients diagnosed in 2008 from three hospitals, including a total of 1629 cases and including only current residents of Sichuan. The median age of diagnosis for cases was 54 years, with a higher proportion of male cases compared with female cases. The most commonly diagnosed subtypes included diffuse large B-cell lymphoma (40.4%), NK/T-cell lymphoma (NKTCL; 11.8%), mixed cellularity Hodgkin lymphoma (7.0%), mantle cell lymphoma (4.8%), and marginal zone B-cell lymphoma (3.9%). Differences in demographic characteristics between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases were apparent for median age at diagnosis (HL: 34 years; NHL: 57 years), and NHLs accounted for nearly all (99.3%) of the 931 cases of extranodal lymphoma. These findings indicate a higher proportion of NKTCL cases and a lower proportion of follicular lymphoma cases (2.3%) in these hospitals in Sichuan, relative to reports from some other provinces within China (e.g., Shanghai and Shanxi) and the USA. Copyright © 2015 John Wiley & Sons, Ltd.

Hypercoagulation and higher fibrinolytic activities occur in patients with colorectal cancer. The operative trauma could enhance the fibrinolysis in the patients with colorectal cancer. The measurement of preoperative D-dimer levels is considered to be useful for predicting lymph node metastasis and stage of colorectal cancer.

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Abstract. The Arg-Gly-Asp (RGD) sequence was selected by using phage-display peptides to target tumors, focusing on targeting ·(v) integrins in tumor blood vessels. Recent studies suggest that peptides containing the RGD sequence can bind to tumor cells, as well as tumor endothelial cells. To investigate whether the RGD peptide has other effects on tumor cells expressing ·(v) integrins, besides its tumor targeting capability, we designed and synthesized a 10-amino peptide that contained the RGD sequence in a cyclic conformation with a disulfide bond, which specifically bound to breast cancer cell lines MDA-MB-231 and MCF-7. We found that this RGD peptide, GCGGRGDGGC, inhibited tumor cell proliferation in a dosedependent manner, and also induced apoptosis and G1-phase cell cycle arrest in both of the cell lines that bound and internalized the peptide. Normal ovarian epithelial cells, which did not bind the RGD peptide, were unaffected. RGD peptide treatment also reduced cell invasiveness in both cell lines in vitro. This study suggests that the RGD peptide not only possesses tumor targeting capacity, but also has direct tumor cytotoxic and invasiveness inhibition effects dependent on the blockage of ·(v) integrin activity, which would make it more efficient in tumor targeting therapy. IntroductionTargeting agents specifically to tumors and their metastases is a central challenge in improving existing cancer detection and therapy. Directing therapeutic agents to tumor cells, tumor blood vessels or tumor lymphatic vasculature is likely to enhance the efficacy of anti-cancer drugs and decrease side effects (1). Different strategies have been pursued to achieve this goal, among which 'homing' peptides are promising alternatives because they bind to surface molecules specific to the tumor, and tumor endothelial and tumor lymphatic cells (2-4), but are smaller than other agents such as antibody fragments, which allow them to easily penetrate tumor tissues. A prominent example for homing peptides is an Arg-Gly-Asp (RGD) sequence that was selected by using phage-display peptides to target tumors, focusing on targeting ·(v) integrins in tumor blood vessels (5). The RGD motif is present in many extracellular matrix components, such as fibronectin and vitronectin, and binds to integrins. Peptides containing the RGD sequence are commonly employed in tumor imaging (6,7) and tumor targeting therapy while coupled with therapeutic agents such as radionucleotides (8,9) and chemotherapeutic drugs (10,11).The RGD-peptide receptor-·(v) integrins are also expressed on the surface of many kinds of tumor cells. Studies indicate that the RGD sequence can bind not only to tumor endothelial cells, but also to tumor cells in vivo (3,12). And in vitro, the RGD peptide can be internalized by tumor cells (13). It is known that ·(v) integrins can mediate adhesion and migration in some tumor cell lines (13) and regulate cell proliferation and survival (14). However, whether the RGD peptide has any direct anti-tumor effects on tumor cells expr...