Comparison of metabolic changes after neoadjuvant endocrine and chemotherapy in ER-positive, HER2-negative breast cancer.

Survival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m2 to 23.87 kg/m2, p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET.

Dimethyl Sulfoxide Enhances Kaposi's Sarcoma-Associated Herpesvirus Production During Lytic Replication.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. In studies of KSHV, efficient virus production and isolation are essential. Reactivation of KSHV can be initiated by treating latently infected cells with chemicals, such as 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. These chemicals have been used as tools to induce lytic replication and viral production in KSHV-producing cell lines. Dimethyl sulfoxide (DMSO) is an organosulfur compound that is frequently used as an aprotic solvent similar to water. In experiments exploring signaling pathways in KSHV-infected cells, DMSO treatment alone as a vehicle affected the lytic gene expression of KSHV. However, to the best of our knowledge, the effects of DMSO on KSHV-producing cells have not yet been reported. Therefore, in this study, we investigated whether DMSO could be used as a reagent to enhance viral production during lytic replication in KSHV-producing cells and assessed the underlying mechanisms. The effects of DMSO on KSHV production were analyzed in iSLK BAC16 cells, which have been widely used for recombinant KSHV production. We found that the production of KSHV virions was significantly increased by treatment with DMSO during the induction of lytic replication. Mechanistically, lytic genes of KSHV were enhanced by DMSO treatment, which was correlated with virion production. Additionally, DMSO induced the phosphorylation of JNK during lytic replication, and inhibition of JNK abolished the effects of DMSO on lytic replication and virion production. Our findings showed that additional treatment with DMSO during the induction of lytic replication significantly improved the yield of KSHV production.