Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition.

PURPOSE: Gynaecological cancer management in older people represents a current challenge. Therefore, in the present paper, we aimed to gather all the evidence reported in the literature concerning gynecological cancers in the elderly, illustrating the state of art and the future perspectives. METHODS: We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS and Grey literature (Google Scholar; British Library) from January 1952 to May 2017, using the terms "ovarian cancer", "endometrial cancer", "cervical cancer", "gynecological cancers" combined with 'elderly', 'cancer', 'clinical trial' and 'geriatric assessment'. RESULTS: The search identified 81 citations, of which 65 were potentially relevant after initial evaluation and met the criteria for inclusion and were analyzed. We divided all included studies into three different issue: "Endometrial cancer", "Ovarian cancer" and "Cervical cancer". CONCLUSIONS: The present literature review shows that, in spite of the higher burden of comorbidities, elderly patients can also benefit from standard treatment to manage their gynecological cancers. It is important to overcome the common habit of undertreating the elderly patients because they are more fragile and with a lower life expectancy than their younger counterpart. Further trials with elderly women are warranted.

A longitudinal study of C1q and anti-C1q autoantibodies in homologous and heterologous pregnancies for predicting pre-eclampsia.

C1q, the recognition molecule of the classical pathway of the complement system, plays a central role in pregnancy. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. C1q can be the target of an antibody response: anti-C1q autoantibodies (anti-C1q) are present in several infectious and autoimmune diseases. The presence of these autoantibodies has been detected also in 2-8% of the general population. Recent evidence indicates that women who undergo assisted reproductive technology (ART) have an increased risk of developing pre-eclampsia (PE), particularly oocyte donation (OD) pregnancies. The aim of this study was to characterize the levels of C1q and anti-C1q in PE gestations, in healthy spontaneous, homologous and heterologous ART pregnancies. Serum of the following four groups of women, who were followed throughout two or three trimesters, were collected: PE, patients diagnosed with PE; OD, oocyte donation recipients; HOM, homologous ART women; Sp, spontaneous physiological pregnancy. Our results indicate that PE patients have lower levels of anti-C1q. In ART pregnant women, the trend of C1q and anti-C1q levels were similar to PE patients, even though these women did not develop PE-like symptoms during pregnancy. This finding suggests an immunological dysfunction at the foetal-maternal interface in ART pregnancies, a hypothesis confirmed by the observation of C1q deposition in placentae derived from OD, comparable to PE. Since significantly lower levels of anti-C1q were detected in PE compared to healthy control sera, we hypothesize the possible binding on placental syncytiotrophoblast microvesicles (STBM), which are increased in the circulation of PE mothers. Furthermore, the characterization of the binding-epitope of anti-C1q revealed that "physiological" autoantibodies were mainly directed against C1q globular domain. We concluded that anti-C1q could have a physiological role in pregnancy: during the healthy spontaneous pregnancy the raised levels of these autoantibodies can be important for the clearance of STBM. In PE and in pathological pregnancies (but also in OD pregnancies), the increase in syncytiotrophoblast apoptosis and consequent increase of the circulating STMB levels lead to a consumption of C1q and anti-C1q.

Phosphoproteins Involved in the Inhibition of Apoptosis and in Cell Survival in the Leiomyoma.

Uterine leiomyomas are benign smooth muscle cell tumors originating from the myometrium. In this study we focus on leiomyoma and normal myometrium phosphoproteome, to identify differentially phosphorylated proteins involved in tumorigenic signaling pathways, and in anti-apoptotic processes and cell survival. We obtained paired tissue samples of seven leiomyomas and adjacent myometria and analyzed the phosphoproteome by two-dimensional gel electrophoresis (2-DE) combined with immobilized metal affinity chromatography (IMAC) and Pro-Q Diamond phosphoprotein gel stain. We used mass spectrometry for protein identification and Western blotting for 2-DE data validation. Quantities of 33 proteins enriched by the IMAC approach were significantly different in the leiomyoma if compared to the myometrium. Bioinformatic analysis revealed ten tumorigenic signaling pathways and four phosphoproteins involved in both the inhibition of apoptosis and cell survival. Our study highlights the involvement of the phosphoproteome in leiomyoma growth. Further studies are needed to understand the role of phosphorylation in leiomyoma. Our data shed light on mechanisms that still need to be ascertained, but could open the path to a new class of drugs that not only can block the growth, but could also lead to a significant reduction in tumor size.

The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner.

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to a chronic inflammatory reaction. It is one of the most widespread gynecological diseases with a 10-15% prevalence in the general female population, rising up to 30-45% in patients with infertility. Although it was first described in 1860, its etiology and pathogenesis are still unclear. It is now accepted that inflammation plays a central role in the development and progression of endometriosis. In particular, it is marked by an inflammatory process associated with the overproduction of an array of inflammatory mediators such as prostaglandins, metalloproteinases, cytokines, and chemokines. In addition, the growth and adhesion of endometrial cells in the peritoneal cavity due to reactive oxygen species (ROS) and free radicals lead to disease onset, its ensuing symptoms-among which pain and infertility. The aim of our review is to evaluate the role of oxidative stress and ROS in the pathogenesis of endometriosis and the efficacy of antioxidant therapy in the treatment and mitigation of its symptoms.

A proteomic approach for the identification of biomarkers in endometrial cancer uterine aspirate.

Endometrial cancer arises from the endometrium. It has a slow progression and a reported survival rate of 75%. The identification of soluble biomarkers in the uterine aspirate may be very useful for its early diagnosis. Uterine aspirates from 10 patients with endometrial cancer and 6 non-endometrial cancer controls were analyzed by two-dimensional gel electrophoresis coupled with mass spectrometry and western blotting for data verification. A total of 25 proteins with fold change in %V ≥2 or ≤0.5 in intensity were observed to change significantly (P<0.05). From the discovery phase, four proteins (costars family protein ABRACL, phosphoglycerate mutase 2, fibrinogen beta chain, annexin A3) were found to be present in the uterine aspirate of endometrial cancers and not in healthy aspirates. Western blotting verification data demonstrated that costars family protein ABRACL, phosphoglycerate mutase 2 were present only in endometrial cancer uterine aspirate while fibrinogen beta chain, annexin A3 were also present in healthy aspirates. To our knowledge, phosphoglycerate mutase 2 has not been previously associated with endometrial cancer. In this study we demonstrate that uterine aspirates are a promising biological fluid in which to identify endometrial cancer biomarkers. In our opinion proteins like costars family protein ABRACL and phosphoglycerate mutase 2 have a great potential to reach the clinical phase after a validation phase.