Hepatocyte nuclear factor (HNF)-1ß and its physiological importance in endometriosis.

Endometriosis is associated with pelvic pain and female infertility. Endometriosis induces inflammation and is vulnerable to oxidative stress damage. To update and summarize the literature concerning the mechanisms that serve to protect genomic DNA from the oxidative damage, the present study reviews the English-language literature for biochemical studies on the transcription factor hepatocyte nuclear factor (HNF)-1ß target genes. Findings demonstrated that retrograde flow of the menstrual blood might give rise to endometriosis. Iron may have a significant impact on endometriosis gene expression. HNF-1ß regulates tissue-specific gene expression in endometriosis, as well as the expression of several genes, including CD44v9, which binds several molecules, including hyaluronan, epidermal growth factor receptor (EGFR), leukemia-associated Rho-guanine nucleotide exchange factor (LARG), IQ motif containing GTPase activating protein 1 (IQGAP1), macrophage migration inhibitory factor (MIF), major histocompatibility complex, class II invariant chain (CD74), cystine transporter subunit (xCT), Fas and extracellular matrix (ECM) proteins. The CD44v9 system is involved in cell migration, growth, survival, anti-apoptosis, immune response and anti-oxidative stress through maintaining higher levels of antioxidants. HNF-1ß may serve to alleviate damage and promote survival of cells experiencing stress by upregulating antioxidant protein expression. This review expands current knowledge on the molecular mechanisms underlying the oxidative stress protection provided by HNF-1ß and provides evidence that elevated HNF-1ß activity might be associated with the CD44v9-dependent signaling cascades.

The biology of uterine sarcomas: A review and update.

Uterine sarcoma is a rare neoplasm, accounting for only 5% of uterine malignancies. The pathogenesis of uterine sarcoma remains largely unknown, although recent basic science and pre-clinical animal models have provided a better understanding of tumor biology. The aim of this study was to review the clinical features, imaging characteristics, genetic aberrations and therapeutic approaches in uterine sarcoma. This study reviewed the English-language literature on clinical and basic studies on uterine sarcoma. The common variants of uterine sarcoma are carcinosarcoma, leiomyosarcoma and endometrial stromal sarcoma (ESS). Genetic profiling efforts have identified amplification, overexpression and mutation, while the molecular mechanisms of tumorigenesis driven by these genomic and genetic aberrations have yet to be fully elucidated yet. Recent genome-wide studies have also identified complex chromosomal rearrangements as oncogenic mechanisms. The cell cycle regulators, p16 and p53, are frequently over-expressed and appear to be involved in key modifications of sarcomagenesis. Molecular-targeted therapy has now been evaluated in clinical trials for certain subtypes. In conclusion, aberrations of cell cycle control would be a critical step in the development of uterine sarcoma. This review has provided new areas of study targeting molecular and genetic pathways.