To investigate the effect of culture pH in the range of 6.85-7.80 on cell growth and erythropoietin (EPO) production at 32.5 and 37.0 degrees C, serum-free suspension cultures of recombinant CHO cells (rCHO) were performed in a bioreactor with pH control. Lowering culture temperature from 37.0 to 32.5 degrees C suppressed cell growth, but cell viability remained high for a longer culture period. Regardless of culture temperature, the highest specific growth rate (mu) and maximum viable cell concentration were obtained at pH values of 7.00 and 7.20, respectively. Like mu, the specific consumption rates of glucose and glutamine decreased at 32.5 degrees C compared to 37.0 degrees C. In addition, they increased with increasing culture pH. Culture pH at 32.5 degrees C affected specific EPO productivity (q(EPO)) in a different fashion from that at 37 degrees C. At 37 degrees C, the q(EPO) was fairly constant in the pH range of 6.85-7.80, while at 32.5 degrees C, the q(EPO) was significantly influenced by culture pH. The highest q(EPO) was obtained at pH 7.00 and 32.5 degrees C, and its value was approximately 1.5-fold higher than that at pH 7.00 and 37.0 degrees C. The proportion of acidic EPO isoforms, which is a critical factor for high in vivo biological activity of EPO, was highest in the stationary phase of growth, regardless of culture temperature and pH. Although cell viability rapidly decreased in death phase at both 32.5 and 37.0 degrees C, the significant degradation of produced EPO, probably by the action of proteases released from lysed cells, was observed only at 37.0 degrees C. Taken together, through the optimization of culture temperature and pH, a 3-fold increase in maximum EPO concentration and a 1.4-fold increase in volumetric productivity were obtained at pH 7.00 and 32.5 degrees C when compared with those at 37.0 degrees C. These results demonstrate the importance of optimization of culture temperature and pH for enhancing EPO production in serum-free, suspension culture of rCHO cells.

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Extramammary Paget disease (EMPD) is a rare intraepithelial malignancy originating in areas rich in apocrine glands, such as the vulva, perineum, perianal area, scrotum, and penis. A few reports of EMPD involving the scrotum have been described in the literature. However, only few reports have described imaging features observed in patients presenting with EMPD. We report EMPD in a patient showing scrotal involvement, focusing on imaging features, particularly those determined ultrasonographically.

The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib with those of TACE alone in patients with locally advanced hepatocellular carcinoma (HCC). Treatment-naïve patients with preserved hepatic reserve (Child–Pugh score ≤ 7) who received TACE plus sorafenib (n = 91) or TACE alone (n = 109) for locally advanced HCC with macrovascular invasion were retrospectively evaluated. Propensity score matching (PSM) was used to correct selection bias, and 63 pairs were created. In the entire study population, the median progression-free survival (PFS) and overall survival (OS) with TACE plus sorafenib were better than those with TACE alone. After PSM, the median PFS (7.0 vs. 4.3 months; p = 0.017) and OS (17.5 vs. 12.8 months; p = 0.049) were again significantly longer with TACE plus sorafenib than with TACE alone. Stratified Cox regression analysis and doubly robust estimation revealed that treatment type was significantly associated with both PFS and OS. In the subgroup analysis, TACE plus sorafenib did not show a significant survival benefit for patients with main portal vein or inferior vena cava invasion. Major complications were similar in both groups (p = 0.330). In conclusion, TACE plus sorafenib showed better survival outcomes than TACE alone in patients with locally advanced HCC.