STAT3 activation in HER2-positive breast cancers: Analysis of data from a large prospective trial
INTERNATIONAL JOURNAL OF CANCER
Authors: Sonnenblick, Amir; Agbor-tarh, Dominique; de Azambuja, Evandro; Hultsch, Susanne; Izquierdo, Miguel; Liu, Minetta; Pruneri, Giancarlo; Harbeck, Nadia; Piccart, Martine; Moreno-Aspita, Alvaro; Granit, Roy Zvi; Rouas, Ghizlane; Fahoum, Ibrahim; Sotiriou, Christos
Abstract
The JAK/STAT3 signaling pathway may be aberrantly activated and have various and conflicting roles in breast cancer. The current study explored prognostic implications of activated STAT3 in human epidermal growth factor receptor 2 (HER2)-positive primary breast cancers in the context of a large prospective study (ALTTO). Activated STAT3 was determined by immunohistochemical analysis of STAT3 phosphorylation (Y705) performed on the primary tumors. This analysis evaluated whether patients with activated STAT3 had disease-free survival (DFS) and overall survival (OS) different from patients without activated STAT3. A total of 5694 patients out of the 8381 patients enrolled in ALTTO were included in this analysis (67.9%), and 2634 of them (46%) had evidence of STAT3 activation (minimum tumor Allred score >= 2). The median follow-up was 6.93 years (6.85-6.97 years), at the end of which 1035 (18.18%) and 520 (9.13%) patients experienced DFS and OS events, respectively. Patients with STAT3 activation experienced improved DFS compared to those without it (multivariable hazard ratio [HR], 0.84; 95% confidence interval [CI] 0.74-0.95; P = .006). There were no group differences in OS (multivariable HR, 0.92; 95% CI 0.78-1.10; P = .37). This effect was limited to ER-positive tumors. In conclusion, these findings support the role of STAT3 activation as a marker of favorable outcome in ER-positive/HER2-positive breast cancer patients.
Effect of vitrification on biogenesis pathway and expression of development-related microRNAs in preimplantation mouse embryos
CELL AND TISSUE BANKING
Authors: Azizi, Elham; Ghaffari Novin, Marefat; Naji, Mohammad; Amidi, Fardin; Hosseinirad, Hossein; Shams Mofarahe, Zahra
Abstract
Vitrification of embryos has been known as the most efficient cryopreservation method in assisted reproductive technology clinics. Vitrification of preimplantation embryo might be associated with altered gene expression profile and biochemical changes of vitrified embryos. Stringent regulation of gene expression in early embryonic stages is very critical for normal development. In the present study, we investigated the effect of vitrification on the canonical miRNA biogenesis pathway, and also the expression of developmental related miRNAs, in 8-cell and blastocyst mouse embryos. Although the expression pattern of the miRNA biogenesis pathway genes differed between 8-cell and blastocyst mouse embryos, vitrification did not affect the expression level of these genes in preimplantation embryos. The expression levels of miR-21 and let-7a were significantly decreased in vitrified 8-cell embryos and fresh blastocysts when compared with fresh 8-cell embryos. The expression of Stat3 was significantly reduced in blastocysts after vitrification. The alteration in the expression pattern of miRNAs, due to their mode of action, can affect broad downstream key developmental signaling pathways. Therefore, the blastocyst stage is the preferred point for embryo vitrification as they are less susceptible to cryo-damages regarding the stability of miRNAs related to the developmental and implantation competence of embryo.