Guidance for peptide vaccines for the treatment of cancer

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system - a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area. Guidance for Peptide Cancer Vaccines

Micronutrient status effects on glucose tolerance in rats

Decrease in bioavailability ofmicronutrients including retinol occurred frequently in patients with diabetes mellitus. We supposed that iron status might relate to glucose metabolism, because vitamin A utilization is inhibited in iron deficiency. To clarify the mechanism of these relationships, following experiment was carried out. Rats were divided into four groups: male wistar-strain rats, which fed the normal diet （N）, the iron-deficient diet （ID）, the retinol-deficient diet （RD）, and Goto-Kakizaki rat （diabetic model rats, GK） fed the normal diet. Every rat was trained to daily meal feeding （9:00-18:00） to measure serum glucose. After 4 weeks of these dietary regiments, serum glucose was higher in iron-deficient rats than the N-group and the RD-group. Hepatic retinol was higher in the ID-group than the GK-group and the N-group. Serum retinol was lower in the ID-group than the GK-group and the N-group. These results suggested that iron deficiency induced glucose intolerance in rats. In conclusion, micronutrients status effect on a diabetic conditio

Starch biosynthesis in rice endosperm requires the presence of either starch synthase I or IIIa

Starch synthase (SS) I and IIIa are the first and second largest components of total soluble SS activity, respectively, in developing japonica rice (Oryza sativa L.) endosperm. To elucidate the distinct and overlapping functions of these enzymes, double mutants were created by crossing the ss1 null mutant with the ss3a null mutant. In the F2 generation, two opaque seed types were found to have either the ss1ss1/SS3ass3a or the SS1ss1/ss3ass3a genotype. Phenotypic analyses revealed lower SS activity in the endosperm of these lines than in those of the parent mutant lines since these seeds had different copies of SSI and SSIIIa genes in a heterozygous state. The endosperm of the two types of opaque seeds contained the unique starch with modified fine structure, round-shaped starch granules, high amylose content, and specific physicochemical properties. The seed weight was ∼90% of that of the wild type. The amount of granule-bound starch synthase I (GBSSI) and the activity of ADP-glucose pyrophosphorylase (AGPase) were higher than in the wild type and parent mutant lines. The double-recessive homozygous mutant prepared from both ss1 and ss3a null mutants was considered sterile, while the mutant produced by the leaky ss1 mutant×ss3a null mutant cross was fertile. This present study strongly suggests that at least SSI or SSIIIa is required for starch biosynthesis in rice endosperm

Barium Promotes Anchorage-Independent Growth and Invasion of Human HaCaT Keratinocytes via Activation of c-SRC Kinase

Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl2) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5–50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5–5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro

Case Study of Text Analytics Applied to Accident Reports of a University

Many accidents have occurred in universities and the accident reports are accumulated in most universities. The information described in the accident reports must be used effectively to prevent a recurrence of the accidents. In this study, we applied text analytics to the description written in 373 accident reports in a university as a case study. Information mining method was adopted for the contents analysis, and 9 factors based on m-SHEL and human error, that is “software”, “hardware”, “environment”, “liveware2”, “management” “slip”, “lapse”, “mistake”, and “violation” were used for morphological analysis for description in report. The factors in each category of accident situation were extracted, and it is suggested that text analytics is one of the most effective methods to analyse the accident reports in universities

Effects of air pollution-related heavy metals on the viability and inflammatory responses of human airway epithelial cells.

Various metals produced from human activity are ubiquitously detected in ambient air. The metals may lead to induction and/or exacerbation of respiratory diseases, but the significant metals and factors contributing to such diseases have not been identified. To compare the effects of each metal and different oxidation states of metals on human airway, we examined the viability and production of interleukin (IL)-6 and IL-8 using BEAS-2B cell line, derived from human airway epithelial cells. Airway epithelial cells were exposed to Mn(2+), V(4+), V(5+), Cr(3+), Cr(6+), Zn(2+), Ni(2+), and Pb(2+) at a concentration of 0.5, 5, 50, or 500 μmol/L for 24 hours. Mn and V decreased the cell viability in a concentration-dependent manner, and V(5+) tended to have a greater effect than V(4+). The Cr decreased the cell viability, and (Cr(+6)) at concentrations of 50 and 500 μmol/L was more toxic than (Cr(+3)). Zn at a concentration of 500 μmol/L greatly decreased the cell viability, whereas Ni at the same concentration increased it. Pb produced fewer changes. Mn and Ni at a concentration of 500 μmol/L induced the significant production of IL-6 and IL-8. However, most of the metals including (V(+4), V(+5)), (Cr(+3), Cr(+6)), Zn, and Pb inhibited the production of both IL-6 and IL-8. The present results indicate that various heavy metals have different effects on toxicity and the proinflammatory responses of airway epithelial cells, and those influences also depend on the oxidation states of the metals

Effects of hydrogen peroxide on mucociliary transport in human airway epithelial cells.

The effects of environmental pollutants on airway clearance have not been well elucidated. This study examined mucociliary transport using different sized-fluorescent particles on polarized human airway epithelial cells which were maintained in an air-liquid interface (ALI) culture system. The effects of hydrogen peroxide (H2O2) exposure on mucociliary transport were also investigated. The movement of fluorescent particles with diameters of 10-14 and 2.5-4.5 µm was observed by fluorescent microscopy as an index of the mucociliary transport. The mixture of the particles with two different sizes was propelled concentrically on the apical surface by the interaction of ciliary activity and mucus in the control condition, whereas H2O2 exposure for 24 h significantly inhibited the movement of the particles. The particle sizes did not affect their movement after the control or H2O2 exposure. These results suggest that particle tracking on polarized human airway epithelial cells is a useful experimental tool for the evaluation of the effect of environmental pollutants on mucociliary transport. In addition, reactive oxygen species may impair mucociliary transport, leading to the airway damage and exacerbation of respiratory diseases