がんの科学と治療

Many cancer survivors report cognitive impairment before, during and after medical treatment. It is well known that many factors other than chemotherapy take part in the development of these cancer- related cognitive impairments (CRCI), such as cancer-related fatigue, psychological as well as molecular factors. The purpose of this review is to describe the impact of physical inactivity in the genesis of these cognitive changes in cancer patients. References for this narrative review comes primarily from PubMed, Cochrane Library and Livivo databases. It contains literature search from October 2003 to April 2016. Our search was focused on available data for the influence of physical inactivity on cognitive performance of cancer patients. Cancer patients have decreased levels of physical activity during treatment. It is suggested that lack of physical activity in general is associated with cognitive decline. At present, most available data comes from trials with heart failure patients as well as results from bed rest studies in space medicine. The development of CRCI is a multifactorial process with physical inactivity appearing to play an important role. However, the available data remains limited and future trials are needed to examine the specific role of physical inactivity on CRCI.

Object: A chemotherapy drug such as cisplatin or diamminedichloroplatinum (DDP) is an alkylating agent that is widely used to treat many cancers despite its associated severe side effects. Biotherapy involving oncolytic adenoviruses also has proven anti-tumor efficacy. Survivin, an inhibitor of apoptosis is highly expressed in tumor cells. The aim of this study was to examine the synergistic effects of combined therapy including Survivin-responsive adenovirus and cisplatin in the treatment of lung cancer and to further reveal the mechanism involved. Methods: Two lung cancer cell lines, NCI-H292 and NCI-H66, were obtained from the cell collections center at CAS-China. A Survivin-responsive conditionally replicating adenovirus (CRAd) with a deleted E1B region was developed in our laboratory. The anti-tumor efficacy of combined in vitro and in vivo treatment (DDP plus CRAd) was assessed with MTS assays and a subcutaneous mouse model, respectively. The expression of Coxsackie adenoviral receptor (CAR) on cancer cell surfaces was determined through RT-PCR analysis. Results: The MTS assays revealed maximal tumor inhibition rates of 70% and 60% obtained when DDP and CRAd were used at doses of 64 μg/ml and 800 MOI, respectively. Nearly identical inhibition was observed with a combined treatment approach (DDP+CRAd) with lower doses of DDP (4 μg/ml) and CRAd (100 MOI). In vivo studies also revealed that tumor suppression was significantly higher in the combined treatment group. RT-PCR analysis showed that CAR expression was much higher in the combined treatment groups. Conclusion: Our study indicates that the combined treatment approach, including survivin promoter-regulated CRAd and DDP, is therapeutically more effective against lung cancer not only because of the synergistic tumorinhibition of the two treatments but also because of the additional tumor-specificity of CRAd resulting from Survivin promoter insertion.

DNA oxidation by oxygen-radicals generated via an iron catalyzed Fenton reaction has been extensively investigated, but little is known about iron localization in the nuclei of mammalian cells. In vitro studies showed the presence of five oxygen and one nitrogen atoms in the inner coordination sphere of the Fe(II)-DNA complex using X-ray absorption spectroscopy (XANES and EXAFS). The identification of ferritin in the nucleus of cultured cells, as well as iron-protein receptors in the nuclear membrane suggests that iron is actively transported into the nucleus. Therefore, pictures from energy-loss spectroscopic imaging (ESI) are included in this mini-review to illustrate the distribution of iron in a fibroblast cell line. These fibroblasts were iron-overloaded by being cultured in a medium containing Fe(III)-nitrilotriacetate (FeNTA). The elemental mapping of iron and phosphorus was coincident in ultrastructures and revealed a significant concentration of both in condensed chromatin; by contrast, the elemental mapping of nitrogen, used as a control, revealed a homogenous distribution across the entire cell. This observed preferential localization was surprising, considering the pro-oxidant status of iron and the importance of maintaining genome integrity. Interestingly, recent published works demonstrates that iron chelators such as genistein and daidzein, derived from soy isoflavones, can attenuate the expression of genes related to increased cancer risk and oxidative damage in the reproductive tract of female mice. In this same sense, mesenchymal stem cells also exhibit antioxidant properties by reducing superoxide, lipid peroxidation, and DNA breaks to healthful levels after transplantation into the brains of stroke prone spontaneously hypertensive rats. Therefore, we bring attention to the use of all potential antioxidants, particularly those with affinity for both iron and DNA, in therapies for several diseases.