Different dosage forms of gonadotropin-releasing hormone agonist with endocrine therapy in premenopausal hormone receptor-positive breast cancer.

BACKGROUND: Despite the wide use of a 3-month gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a 1-month GnRH agonist regimen when combined with selective estrogen receptor modulators or aromatase inhibitors, especially in younger patients. METHODS: This retrospective cohort study included 1109 premenopausal hormone receptor-positive breast cancer patients treated with GnRH agonist plus selective estrogen receptor modulator or aromatase inhibitor. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1-month or 3-month GnRH agonist in cohorts and different subgroups was analyzed. RESULTS: Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1-month and 3-month groups achieved more than 90% E2 inhibition within 24 months (94.53% vs 92.84%, with a 95% confidence interval for the difference ranging from -4.78% to 1.41%), confirming the noninferiority of 3-month GnRH agonist. Both 1-month and 3-month GnRH agonist rapidly and consistently reduced E2 levels. Of the patients, 60 (6.3%) experienced incomplete ovarian function suppression, with similar rates in the 1-month and 3-month groups (5.5% vs 7.2%). Incomplete ovarian function suppression mainly occurred within the first 12 months, with age younger than 40 years and no prior chemotherapy being the risk factors. Similar disease-free survival and overall survival were found in the 1-month and 3-month groups and in patients with complete and incomplete ovarian function suppression (P > .05). CONCLUSIONS: The ovarian function suppression with 3-month GnRH agonist was not inferior to that with 1-month GnRH agonist, regardless of age or combination with a selective estrogen receptor modulator or an aromatase inhibitor.

Intraspecific variation in genome size in Artemisia argyi determined using flow cytometry and a genome survey.

Different collections and accessions of Artemisia argyi (Chinese mugwort) harbour considerable diversity in morphology and bioactive compounds, but no mechanisms have been reported that explain these variations. We studied genome size in A. argyi accessions from different regions of China by flow cytometry. Genome size was significantly distinct among origins of these 42 Chinese mugwort accessions, ranging from 8.428 to 11.717 pg. There were no significant intraspecific differences among the 42 accessions from the five regions of China. The clustering analysis showed that these 42 A. argyi accessions could be divided into three groups, which had no significant relationship with geographical location. In a genome survey, the total genome size of A. argyi (A15) was estimated to be 7.852 Gb (or 8.029 pg) by K-mer analysis. This indicated that the results from the two independent methods are consistent, and that the genome survey can be used as an adjunct to flow cytometry to compensate for its deficiencies. In addition, genome survey can provide the information about heterozygosity, repeat sequences, GC content and ploidy of A. argyi genome. The nuclear DNA contents determined here provide a new reference for intraspecific variation in genome size in A. argyi, and may also be a potential resource for the study of genetic diversity and for breeding new cultivar.

LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer.

Cyclin D1 is one of the most important oncoproteins that drives cancer cell proliferation and associates with tamoxifen resistance in breast cancer. Here, we identify a lncRNA, DILA1, which interacts with Cyclin D1 and is overexpressed in tamoxifen-resistant breast cancer cells. Mechanistically, DILA1 inhibits the phosphorylation of Cyclin D1 at Thr286 by directly interacting with Thr286 and blocking its subsequent degradation, leading to overexpressed Cyclin D1 protein in breast cancer. Knocking down DILA1 decreases Cyclin D1 protein expression, inhibits cancer cell growth and restores tamoxifen sensitivity both in vitro and in vivo. High expression of DILA1 is associated with overexpressed Cyclin D1 protein and poor prognosis in breast cancer patients who received tamoxifen treatment. This study shows the previously unappreciated importance of post-translational dysregulation of Cyclin D1 contributing to tamoxifen resistance in breast cancer. Moreover, it reveals the novel mechanism of DILA1 in regulating Cyclin D1 protein stability and suggests DILA1 is a specific therapeutic target to downregulate Cyclin D1 protein and reverse tamoxifen resistance in treating breast cancer.