Outcomes During Early Implementation of Mifepristone-Buccal Misoprostol Abortions up to 63 Days of Gestation in a Canadian Clinical Setting.

OBJECTIVE: In January 2017, mifepristone became available in Canada. The goal of this study was to determine the effectiveness and safety of mifepristone-misoprostol abortion during its early implementation in a Canadian setting. METHODS: This retrospective chart review included the first 477 patients who had a mifepristone-misoprostol abortion from March 13 to October 31, 2017, in an urban sexual health clinic. Women with pregnancies up to 63days of gestation had an initial dating ultrasound and ß-human chorionic gonadotropin determination. They were provided mifepristone 200 mg orally in clinic, followed 24-48hours later with misoprostol 800 µg buccally at home. Follow-up, 7-14days later, in clinic or by telephone, used symptom review and follow-up ß-human chorionic gonadotropin or ultrasound. The primary outcome was successful abortion, defined as expulsion of pregnancy without uterine aspiration. RESULTS: Of 477 consecutive mifepristone abortions, 422 women (88.5%) had documented follow-up, with 408 (96.7%) successful abortions, including eight in women who had a repeat dose of misoprostol. Fourteen (3.3%) unsuccessful abortions required uterine aspiration, two (0.5%) for ongoing pregnancy and 12 (2.8%) for incomplete abortion or persistent bleeding. Seventeen women (4.0%) had emergency department visits, one (0.2%) of whom was hospitalized and three (0.7%) of whom received blood transfusion. Four women (1.0%) were treated for infection. CONCLUSION: Mifepristone-misoprostol medical abortion was safe and effective during early implementation in Canada, comparable to previously published outcomes.

CD24(+) cells fuel rapid tumor growth and display high metastatic capacity.

INTRODUCTION: Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epithelial cells isolation, recently it was suggested as a potential prognostic marker in a wide variety of malignancies. Here, we demonstrate that CD24(+) cells create intra-tumor heterogeneity, and display highly metastatic properties. METHODS: The mammary carcinoma Mvt1 cells were sorted into CD24(-) and CD24(+) cells. Both subsets were morphologically and phenotypically characterized, and tumorigenic capacity was assessed via orthotopic inoculation of each subset into the mammary fat pad of wild-type and MKR mice. The metastatic capacity of each subset was determined with the tail vein metastasis assay. The role of CD24 in tumorigenesis was further examined with shRNA technology. GFP-labeled cells were monitored in vivo for differentiation. The genetic profile of each subset was analyzed using RNA sequencing. RESULTS: CD24(+) cells displayed a more spindle-like cytoplasm. The cells formed mammospheres in high efficiency and CD24(+) tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24- cells. Interestingly, CD24-KD in CD24+ cells had no effect both in vitro and in vivo on the various parameters studied. Moreover, CD24(+) cells gave rise in vivo to the CD24(-) that comprised the bulk of the tumor. RNA-seq analysis revealed enrichment of genes and pathways of the extracellular matrix in the CD24(+) cells. CONCLUSION: CD24(+) cells account for heterogeneity in mammary tumors. CD24 expression at early stages of the cancer process is an indication of a highly invasive tumor. However, CD24 is not a suitable therapeutic target; instead we suggest here new potential targets accounting for early differentiated cancer cells tumorigenic capacity.

Highly specific role of the insulin receptor in breast cancer progression.

Accumulating evidence from clinical trials indicates that specific targeting of the IGF1 receptor (IGF1R) is not efficient as an anti-breast cancer treatment. One possible reason is that the mitogenic signals from the insulin receptor (IR) can be processed independently or as compensation to inhibition of the IGF1R. In this study, we highlight the role of the IR in mediating breast tumor progression in both WT mice and a hyperinsulinemic MKR mouse model by induction of Ir (Insr) or Igf1r knockdown (KD) in the mammary carcinoma Mvt-1 cell line. By using the specific IR antagonist-S961, we demonstrated that Igf1r-KD induces elevated responses by the IR to IGF1. On the other hand, Ir-KD cells generated significantly smaller tumors in the mammary fat pads of both WT and MKR mice, as opposed to control cells, whereas the Igf1r-KD cells did not. The tumorigenic effects of insulin on the Mvt-1 cells were also demonstrated using microarray analysis, which indicates alteration of genes and signaling pathways involved in proliferation, the cell cycle, and apoptosis following insulin stimulation. In addition, the correlation between IR and the potential prognostic marker for aggressive breast cancer, CD24, was examined in the Ir-KD cells. Fluorescence-activated cell sorting (FACS) analysis revealed more than 60% reduction in CD24 expression in the Ir-KD cells when compared with the control cells. Our results also indicate that CD24-expressing cells can restore, at least in part, the tumorigenic capacity of Ir-KD cells. Taken together, our results highlight the mitogenic role of the IR in mammary tumor progression with a direct link to CD24 expression.