RESUMO
Ectopic pregnancies, implantation of a fertilized ovum in any location other than within the endometrial cavity, occur in 1-2% of all pregnancies. Despite current enhanced early diagnosis enabled by serum beta-human choriogonadotropin (hCG) levels and high-resolution ultrasound, this clinical entity continues to account for between 2.7 and 6% of all maternal deaths. The most common site of ectopic implantation is the Fallopian tube (>90% of cases), and less commonly in previous Cesarean scar, ovary, cervix, or the abdomen. Complete tubal abortion refers to a tubal pregnancy having been expelled from the distal portion of the Fallopian tube into the peritoneal cavity and may be associated with either considerable hemorrhage, spontaneous resolution, or rarely serve as an initial nidus for an abdominal pregnancy. We present unusual sonographic findings of a complete tubal abortion in a patient with minimal symptomology.
RESUMO
Placenta accreta spectrum (PAS) defined by various degrees of abnormally invasive placentation is strongly associated with severe maternal morbidity and maternal mortality, mainly reflecting maternal hemorrhage. Predisposing factors for this condition include: multiparity, placenta previa, previous uterine surgeries (previous curettage, cesarean delivery, and myomectomy), smoking and previous PAS. Prenatal sonographic findings associated with PAS include the presence of placenta previa, loss of the hypoechoic retroplacental sonolucency, myometrial thinning, interruption of the irregularity of the bladder wall, excessive vascularity of the uterovesical plane, placental lacunae, increased placental vascularity, bridging vessels with vascularity extending from the placental bed across the uterine wall into the bladder or other pelvic organs. PAS is very rare among nulliparous patients, especially those without previous uterine surgery. We describe an unusual case of PAS in a nulliparous patient with an unscarred uterus and systemic lupus erythematosus in whom a fundal placenta with PAS and thinned and areas of absent myometrium suspected at midtrimester sonography, sustained uterine atony and severe hemorrhage at delivery, necessitated massive blood transfusion and subtotal hysterectomy. Both mother and infant did well. Pathology confirmed PAS and marked uterine thinning. Although PAS most commonly is associated with placenta previa and the presence of previous cesarean delivery, this case emphasizes the need for alertness of at times subtle prenatal sonographic findings of PAS irrespective of placental location even among nulliparous patients, especially those with systemic lupus erythematosus.
RESUMO
MicroRNAs have been shown to play important roles in breast cancer progression and can serve as biomarkers. To assess the prognostic role of a panel of miRNAs in breast cancer, we collected plasma prospectively at the time of initial diagnosis from 1,780 patients with stage I-III breast cancer prior to definitive treatment. We identified plasma from 115 patients who subsequently developed distant metastases and 115 patients without metastatic disease. Both groups were matched by: age at blood collection, year of blood collection, breast cancer subtype, and stage. The median follow up was 3.4 years (range, 1-9 years). We extracted RNA from plasma and analyzed the expression of 800 miRNAs using Nanostring technology. We then assessed the expression of miRNAs in primary and metastatic breast cancer samples from The Cancer Genome Atlas (TCGA). We found that, miR-24-3p was upregulated in patients with metastases, both in plasma and in breast cancer tissues. Patients whose primary tumors expressed high levels of miR-24-3p had a significantly lower survival rate compared to patients with low mir-24-3p levels in the TCGA cohort (n=1,024). RNA-Seq data of the samples with the highest miR-24-3p expression versus those with the lowest miR-24-3p in the TCGA cohort identified a specific gene expression signature for those tumors with high miR-24-3p. Possible target genes for miR-24-3p were predicted based on gene expression and binding site, and their effects on cancer pathways were evaluated. Cancer, breast cancer and proteoglycans were the top three pathways affected by miR-24-3p overexpression.
RESUMO
The activity of the E3 ligase, SMURF2, is antagonized by an intramolecular, autoinhibitory interaction between its C2 and Hect domains. Relief of SMURF2 autoinhibition is induced by TGFß and is mediated by the inhibitory SMAD, SMAD7. In a proteomic screen for endomembrane interactants of the RING-domain E3 ligase, RNF11, we identified SMURF2, among a cohort of Hect E3 ligases previously implicated in TGFß signaling. Reconstitution of the SMURF2·RNF11 complex in vitro unexpectedly revealed robust SMURF2 E3 ligase activity, with biochemical properties previously restricted to the SMURF2·SMAD7 complex. Using in vitro binding assays, we find that RNF11 can directly compete with SMAD7 for SMURF2 and that binding is mutually exclusive and dependent on a proline-rich domain. Moreover, we found that co-expression of RNF11 and SMURF2 dramatically reduced SMURF2 ubiquitylation in the cell. This effect is strictly dependent on complex formation and sorting determinants that regulate the association of RNF11 with membranes. RNF11 is overexpressed in certain tumors, and, importantly, we found that depletion of this protein down-regulated gene expression of several TGFß-responsive genes, dampened cell proliferation, and dramatically reduced cell migration in response to TGFß. Our data suggest for the first time that the choice of binding partners for SMURF2 can sustain or repress TGFß signaling, and RNF11 may promote TGFß-induced cell migration.
