Cytogenetic analysis of epithelial ovarian cancer's stem cells: an overview on new diagnostic and therapeutic perspectives.

Ovarian cancer is one of the most frequent solid tumor that shows clearly biphasic behaviour in response to chemotherapy, with the majority of patients who achieved complete remission after the first cycle of chemotherapy, and subsequently present a relapse which, in most cases, leads to death. Epithelial ovarian cancer (EOC) arises as a consequence of genetic alterations that affect the cells of the ovarian surface, which leads to changes that occur through the activation of oncogenes and inactivation of tumor suppressor genes. The progression of EOC is characterized by a series of combined epigenetic aberrations, including the most important of those determined by the loss of methylation of certain regions of DNA encoding genes such as Ras-association domain-containing family 1 [(RASSF1A) tumor suppressor], death-associated protein kinase [(DAPK) protein kinase associated with the regulation of apoptosis], human sulfa- tase-I [(hSulf-1) sulfatase, which plays a key role in the regulation of apoptosis], breast cancer 1 gene [(BRCA1) tumor suppressor gene, involved in the processes of DNA repair], and HOXAI0 (gene required to promote many transcription factors). To date, accumulating evidence suggests that the initial clinical response is due primarily to the therapeutic efficacy of chemotherapy against differentiated can- cer cells that constitute the bulk of the tumor, whereas the high rate of recurrence is thought to be due to remaining drug-resistant cells, biologically distinct, identified as cancer stem cells (CSC). Current efforts are focusing on genetic and cytological definition of CSC, to guide the development of new diagnostic, and therapeutic perspectives.

Post-partum management in a patient affected by thrombotic thrombocytopenic purpura: case report and review of literature.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially lethal syndrome characterized by severe thrombocytopenia, microangiopathic haemolytic anaemia, and aspecific neurologic symptoms. This syndrome is the result of an abnormal intravascular platelet aggregation which induces transient ischemia in various organs, especially in the central nervous system. Platelet aggregation causes also fragmentation of erythrocytes, thus leading to the characteristic anaemia. The exact cause of TTP is unknown, but a large body of evidence suggest that this syndrome might be due to acquired (immunological) or congenital ADAMTS13 deficiency. The dysregulation of ADAMTS 13 activity could promote massive release of high molecular weight multimers of von Willebrand factor (VWF) from endothelium and, as a consequence, could cause intravascular platelet aggregation. Pregnancy is commonly associated with numerous metabolic, immunological, and haemostatic changes which could increase thrombotic risk: during pregnancy, in fact, it is generally observed an increase of procoagulant activity and a decrease of fibrinolytic activity; moreover, at the end of pregnancy, it is not rare to find thrombocytopenia. All these reasons lead us to consider pregnancy itself as a triggering event for the onset of TTP. The authors describe a case of TTP occurred during puerperium, in a patient who underwent caesarean section.

Impairment of lymphocyte sensitivity to prostaglandin E2 in cultures from patients with lymphoadenopathy associated syndrome.

Prostaglandin E2 (PGE2) appears to have an immunosuppressive role in human immunodeficiency virus (HIV) infection. Therefore, the effect was studied of PGE2 pretreatment of T lymphocytes from patients with lymphadenopathy associated syndrome (LAS) on the expression of CD25 and CD71 as well as plaque forming cell (PFC) generation in pokeweed mitogen (PWM)-driven cultures. The PGE2-treated or untreated T lymphocytes were cultured with B cells and monocytes in the presence of PWM. Both CD25 and CD71 expression were assessed with an immunofluorescence technique; PFC generation was tested by hemolysis. Before exposure to PWM, LAS lymphocytes showed activation as evidenced by high CD25 and CD71 expression and PFC generation. Pretreatment by PGE2 did not inhibit expression of activation markers and PFC generation in LAS cultures, in contrast to what happened in control cultures. Thus, LAS lymphocytes are activated in vivo and are less sensitive to PGE2 inhibition than normal lymphocytes.

A short incubation with PGE2 affects the proliferative response of T lymphocytes to PWM.

In this study we have investigated the role of PGE2 in the activation of human T lymphocytes by PWM. A preincubation of these cells with molar concentrations of the prostaglandin ranging from 10(-9) M to 10(-4) M is able to reduce the expression of IL-2R and CD71 on T lymphocyte membrane during the first days of culture, while the DR molecule which is expressed later in the same experimental conditions is not affected by the treatment of T lymphocytes with PGE2. The PGE2-induced inhibition of IL-2R and CD71 well correlates with the reduction of 3H-thymidine incorporation by T cells, indicating that a preincubation of T lymphocytes with PGE2 profoundly affects the proliferative apparatus of these cells when they are stimulated by PWM.

Prostaglandin E2-induced inhibition of the in vitro immune response by SRBC-stimulated human lymphocytes.

Exogenous PGE2 strongly inhibits the response of human lymphocyte cultures to SRBC. This effect is mediated through a T cell inhibition since non-T cells are not significantly affected. Indomethacin, which inhibits in this system lymphocyte endogenous PGE2 synthesis increases the in vitro immune response. The effect of indomethacin is overcame by exogenous PGE2. These data may be relevant for explaining the immunomodulatory role of PGE2 following antigen challenge.