Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients.

PURPOSE: Scalp cooling during chemotherapy infusion to mitigate alopecia for breast cancer patients is becoming widespread; however, studies regarding hair recovery after chemotherapy with scalp cooling are limited. We conducted a prospective study of hair recovery after chemotherapy with scalp cooling. PATIENTS AND METHODS: One hundred and seventeen Japanese female breast cancer patients who completed planned (neo)adjuvant chemotherapy using the Paxman Scalp Cooling System for alopecia prevention were evaluated for alopecia prevention in our prospective study. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after chemotherapy. Primary outcomes were grades of alopecia judged by two investigators (objective grades) and patients' answers to the questionnaire regarding the use of a wig or hat (subjective grades). RESULTS: Of 117 patients, 75 completed scalp cooling during the planned chemotherapy cycles (Group A), but 42 discontinued it mostly after the first cycle (Group B). Objective and subjective grades were significantly better in Group A than in Group B throughout 1 year, and at 4 and 7 months after chemotherapy. When we restricted patients to those with objective Grade 3 (hair loss of > 50%) at 1 month, Group A exhibited slightly faster hair recovery based on the objective grades than Group B. There was less persistent alopecia in Group A than in Group B. CONCLUSIONS: Scalp cooling during chemotherapy infusion for Japanese breast cancer patients increased the rate of hair recovery and had preventive effects against persistent alopecia.

Proteasome inhibitor MG132 induces NAG-1/GDF15 expression through the p38 MAPK pathway in glioblastoma cells.

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is regulated by the p53 and Egr-1 tumor suppressor pathways. Many anti-cancer drugs and chemicals induce NAG-1 expression, but the mechanisms are not fully understood. Transgenic mice expressing human NAG-1 are resistant to intestinal and prostate cancer, suggesting that NAG-1 is a tumor suppressor. Proteasome inhibitors exhibit anti-glioblastoma activities in preclinical studies. Here, we show that the proteasome inhibitors MG132 and bortezomib induced NAG-1 expression and secretion in glioblastoma cells. MG132 increased NAG-1 expression through transcriptional and post-transcriptional mechanisms. At the transcriptional level, the induction of NAG-1 required the -133 to +41 bp region of the promoter. At post-transcriptional levels, MG132 stabilized NAG-1 mRNA by increasing the half-life from 1.5 h to >8 h. Because of the dramatic increase in mRNA stability, this is likely the major contributor to MG132-mediated NAG-1 induction. Further probing into the mechanism revealed that MG132 increased phosphorylation of the p38 MAPK pathway. Consequently, inhibiting p38 phosphorylation blocked activation of the NAG-1 promoter and decreased mRNA stability, indicating that p38 MAPK activation mediates both MG132-dependent promoter activation and mRNA stabilization of NAG-1. We propose that the induction of NAG-1 by p38 MAPK is a potential contributor to the anti-glioblastoma activity of proteasome inhibitors.

Uptake of methacrolein and methyl vinyl ketone by tree saplings and implications for forest atmosphere.

Methacrolein (MACR) and methyl vinyl ketone (MVK) are oxygenates produced from isoprene which is abundantly emitted by trees. The uptake rate of these compounds by leaves of three different Quercus species, Q. acutissima, Q. myrsinaefolia, and Q. phillyraeoides, at typical concentrations within a forest (several part per billion by volume) were determined. The rates of uptake of croton aldehyde (CA) and methyl ethyl ketone (MEK) were also investigated for comparison. The rates of uptake of the two aldehydes MACR and CA were found to be higher than those of the two ketones. In particular, the rate of MEK uptake for Q. myrsinaefolia was exceptionally low. The ratio of intercellular to fumigated concentrations, Ci/Ca, for MACR and CA was found to be low (0-0.24), while the ratio for the two ketones was 0.22-0.90. To evaluate the contribution of tree uptake as a sink for the two isoprene-oxygenates within the forest canopy, loss rates of the compounds due to uptake by trees and by reactions with hydroxyl radicals (OH radicals) and O(3) were calculated. The loss rate by tree uptake was the highest, followed by the reaction with OH radicals, even at a high OH concentration (0.15 pptv) both for MACR and MVK, suggesting that tree uptake provides a significant sink.