Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.
An improvement in photodynamic therapy (PDT) efficiency against a human gastric cancer cell line (MKN45) with 5-aminolevulinic acid (ALA) and lanthanide nanoparticles (LNPs) is described. An endogenous photosensitizer, protoporphyrin IX, biosynthesized from ALA and selectively accumulated in cancer cells, is sensitizable by the visible lights emitted from up-conversion LNPs, which can be excited by a near-infrared light. Ten kinds of surface modifications were performed on LNPs, NaYF4(Sc/Yb/Er) and NaYF4(Yb/Tm), in an aim to distribute these irradiation light sources near cancer cells. Among these LNPs, only the amino-functionalized LNPs showed affinity to MKN45 and HeLa cancer cells. A PDT assay with MKN45 demonstrated that amino-modified NaYF4(Sc/Yb/Er) gave rise to a dramatically enhanced PDT effect, reaching almost perfect lethality, whereas NaYF4(Yb/Tm)-based systems caused little improvement in PDT efficiency. The improvement of PDT effect with the amino-modified NaYF4(Sc/Yb/Er) is promising for a practical PDT against deep cancer cells that are reachable only by near-infrared lights.
Improving productivity is an urgent issue in the swine industry if it is to compete internationally. However, lack of data about recent productivity transition obstructs stakeholder planning. This study investigated the yearly productivity trends among farrow-tofinish swine farms in Japan using annual productivity data from 2013-2018 obtained for 70 farms in Japan. The productivity parameters analyzed were pigs born alive per litter (PBA), preweaning mortality (PRWM), pigs weaned per litter (PWL), litters per mated female per year (LMFY), pigs weaned per mated female per year (PWMFY), post-weaning mortality (POWM) and marketed pigs per mated female per year (MP). Data were classified into three groups based on the size of the average female inventory and compared among groups. Results presented the mean PBA increased continuously over the 6-year period (P < 0.001), and the PWL, PWMFY, and MP means began increasing after 2015 (P < 0.001). These upward trends were particularly remarkable on large farms. The mean PRWM increased sharply in 2014, thus inhibiting the increases in PWL, PWMFY, and MP for the same year. The LMFY and POWM means did not change during the study period. Altogether, productivity in Japan improved markedly during the study period, indicating highly prolific sows were well utilized with suitable breeding techniques among farmers these days. Continued genetic improvement and sow management would aid further development in Japan.
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