PM penetrates into the barrier-disrupted skin, causing inflammation, demonstrating detrimental effects in the skin.

Variable sizes of nanoparticles, ranging from nano to micro scale, are of toxicological interest. In the present study, the authors hypothesized that, in addition to the size, the shape of iron oxide (Fe2O3) nanoparticles is a major factor that contributes to particle cytotoxicity. Cytotoxicity to mouse macrophage cells (RAW 264.7) was investigated using 3 different particles: micro-sized Fe2 O3 (M-Fe2O3), nano-sized Fe2O3 (N-Fe2O3), and rod-shaped Fe2O3 (R-Fe2O3). Whereas M-Fe2O3 and N-Fe2O3 were located in the vacuole as aggregates, R-Fe2 O3 was often spread throughout the cytoplasm. The extent of cytotoxicity measured by the water soluble tetrazolium (WST-1) assay was in the order R-Fe2O3 ≈ N-Fe2O3 > M-Fe2O3, whereas the extent revealed by the lactate dehydrogenase assay was in the order R-Fe2O3 >> N-Fe2O3 ≈ M-Fe2 O3. In addition, the degree of tumor necrosis factor-α and reactive oxygen species (ROS) production was in the order of R-Fe2O3 > N-Fe2 O3 > M-Fe2O3. In addition, a much higher extent of necrosis was associated with the presence of R-Fe2O3. These results suggest that the higher degree of necrosis due to R-Fe2O3 is correlated with both the higher degree of membrane damage and ROS production by R-Fe2O3 compared with the results of the other Fe2O3 particles. These results also showed that the degree of cytotoxicity of nanoparticles should be evaluated based on shape as well as size, because changes in shape and size are accompanied by alterations in surface area, which relate closely to cytotoxicity.

BackgroundInternational clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries.MethodsA questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials.ResultsThe number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH.ConclusionsOur results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to encourage doctors to participate in and conduct clinical trials.

Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.