A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study*

A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer

Gynecologic Oncology Group Study 229C: Personal Reflection

I heard the statistician say, “The drug does not have sufficient activity to study further in this population.” It was my co-investigator on GOG study 229C, Gefitinib in the Treatment of Advanced and Recurrent Endometrial Cancer (see related extended abstract in this issue*), calling from Roswell Park in Buffalo. He had just completed the analysis of data from 26 women treated on our study – a study which had been five years in the making from concept to clinical trial

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study*

A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer

The Oncoplacental Gene Placenta-Specific Protein 1 Is Highly Expressed in Endometrial Tumors and Cell Lines

Placenta-specific protein 1 (PLAC1) is a small secreted protein expressed exclusively in trophoblast cells in the mammalian placenta. PLAC1 is expressed early in gestation and is maintained throughout. It is thought to function in trophoblast invasion of the uterine epithelium and, subsequently, to anchor the placenta to the epithelium. In recent years, evidence has accumulated that PLAC1 is also expressed in a variety of human solid tumors, notably in breast cancers. We demonstrate for the first time that PLAC1 is ubiquitously expressed in tumors originating in uterine epithelium. Further, we find that PLAC1 expression is significantly higher in the more advanced, more aggressive endometrial serous adenocarcinomas and carcinosarcomas relative to endometrioid adenocarcinomas by more than 6-fold and 16-fold, respectively. We also show that PLAC1 is simultaneously transcribed from two promoters but that, in all cases, the more distal P1 promoter dominates the more proximal P2 promoter. While the function of the two PLAC1 promoters and their regulation are as yet unknown, overall expression data suggest that PLAC1 may serve as a biomarker for endometrial cancer as well as a potential prognostic indicator

Atypical hemolytic uremic syndrome in the postpartum period: a case series

Background: Atypical hemolytic uremic syndrome (aHUS) may present in either the antepartum or postpartum period and is often indistinguishable from other pregnancy-associated diseases. Timely recognition and appropriate treatment can greatly reduce maternal morbidity and mortality. Cases: This case series describes two cases of aHUS in the post-partum period, the difficulty in distinguishing the diagnosis, and the implementation of appropriate treatment with eculizumab, a terminal complement inhibitor. Conclusion: As a terminal complement inhibitor, eculizumab, has been shown to significantly improve clinical and long term renal outcomes, early diagnosis of aHUS is increasingly important. These two cases of aHUS demonstrate the path of accurate diagnosis and timely initiation of therapy to maximize the possibility of patient recovery

MiR-888: A newly identified miRNA significantly over-expressed in endometrial cancers

Endometrial cancer is the most common gynecological malignancy and the fourth most common cancer in women. With accumulating evidence, microRNAs have emerged as significant players in the development and progression of cancers. The data points to miR-888 playing an important functional role in the development of aggressive endometrial tumors. Future research will focus on identifying and validating the targets of miR-888 to elucidate its mechanism of action and support this hypothesi

Combination therapy with mTOR and PI3 kinase inhibitors is broadly synergistic in a wide variety of endometrial cancer cells

Dysregulation of mammalian target of rapamycin (mTOR) signaling has been found in many human tumors, including endometrial cancer, and mTOR inhibitors have been utilized in clinical trials as targeted therapies with only limited success. Herein we identify a viable treatment alternative that overcomes temsirolimus-induced AKT phosphorylation in endometrial cancer. Our data suggest temsirolimus and BEZ235 inhibit different components of the AKT/mTOR signaling pathway to accomplish synergistic pathway inhibition, which is necessary for therapeutic efficacy to abrogate the increased signaling through AKT that occurs with mTOR inhibition alon

Toward a microRNA signature of endometrial cancer

A simple meta-analysis of eight microRNA (miRNA) expression surveys of endometrial cancers reveals a panel of sixteen miRNAs that are significantly over-expressed (n = 15) or under-expressed (n = 1) in at least three surveys. Examination of these miRNAs indicates that they target mRNAs involved in a number of basic cellular processes including the crucial epithelial to mesenchymal transition (EMT) and hypoxia response. The central role played by these miRNAs is reinforced by the demonstration that they are all among the most ancient of all animal miRNAs. This suggests that they are members of a core set of miRNAs dysregulated as part of the carcinogenic cellular reprogramming process

Knockdown of MTDH increases drug sensitivity to HDAC inhibitor and TRAIL combination treatment in endometrial cancer cells

Understanding the molecular mechanisms of chemoresistance is vital to design therapies to restore chemosensitivity. MTDH mediates drug resistance by regulating expression of genes required for the control of apoptosis and cell cycle. These findings indicate that sensitivity to chemotherapy agents and combination treatment with HDAC inhibitor and TRAIL can be restored by manipulating MTDH, and hence depletion of MTDH is a potentially novel avenue for effective cancer therapy