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.

Effect of prostaglandins on Fc-IgG receptors of human circulating T and B lymphocytes.

A short preincubation of human T and B lymphocyte subpopulations with physiologic or pharmacologic concentrations of PGs E2 and F1 alpha, but not with E1 and F2 alpha, markedly depresses the cell ability to bind immune complexes, through FcR-IgG. This effect appears to be relatively temperature-independent. These observations indicate that PG treatment of human lymphocytes may be useful to distinguish the subclasses of FcR-IgG-bearing T and B cells, which are sensible to the modulating effect of PGs.

Effect of cyclooxygenase inhibitors on PGE2-sensitive human lymphocyte receptors.

A short preincubation of human T and B lymphocyte populations with exogenous Prostaglandin E2 (PGE2) markedly depresses the expression of surface receptors binding the Fc portion of IgG, sheep and mouse erythrocytes (FcR-IgG, Ea and ME receptors respectively). Using two cyclooxygenase inhibitors (indomethacin and meclofenamate) it is shown that endogenous PGE2 does not modify the activity of these lymphocyte surface receptors. The lymphocyte sensitivity to exogenous PGE2, which is released under various physiologic and pathologic stimuli, may represent present another method to subdivide human lymphocytes in distinct subsets.

Effect of prostaglandin E2 on pokeweed mitogen-activated human lymphocyte cultures.

It is shown that a short incubation of peripheral human lymphocytes with PGE2 is able to reduce the B cell differentiation induced by PWM. The target of PGE2 action appears to belong to T lymphocytes, since the treatment of non-T cells is uneffective in reducing the immune response. Both OKT4+ and OKT8+ subsets are sensitive to PGE2. Data concerning the role of endogenous as well as exogenous PGE2 either on unfractionated or fractionated OKT4+, OKT8+ and non-T lymphocytes are also discussed. The PGE2 inhibition on immunoglobulin synthesis in PWM-stimulated cultures seems to be mediated by a complex effect on both the T cell subsets.

Interaction between prostaglandins and human T lymphocytes: effect of PGE2 on E-receptor expression.

E-rosette formation is not modified by preincubation of lymphocytes with prostaglandins (PGs) E1, F1 alpha, and F2 alpha. On the contrary, short preincubation with PGE2 affects active rosette-forming cells (Ea-RFC) and, only slightly, total RFC. This effect appears to be dose-dependent and relatively temperature-independent; it does not require calcium ions. Incubation with a fraction enriched in late RFC showed that PGE2 does not affect late rosette formation. It is postulated that PGE2 may redistribute surface receptors for sheep erythrocytes on T lymphocyte membranes. Thus, sensitivity to PGE2 may be considered another difference between early and late RFC.

Spontaneous rosette-forming lymphocyte sensitivity to prostaglandins in patients with cervical carcinoma after surgery.

We have reported a marked decrease of lymphocyte sensitivity to prostaglandins (PGs) in patients with untreated cervical carcinoma and other solid neoplasias. Particularly, Ea and ME rosette formation was inhibited only slightly by PGs in all cancer patients studied, as compared with the high inhibition values observed in normal individuals (Clin Immunol Immunopathol, 1981). In the present work, the PG-induced inhibition of Ea and ME rosette formation has been studied in patients with stage 0 cervical carcinoma up to 180 days after hysterectomy. It has been found that in these patients the PG sensitivity increased gradually up to or higher than the levels seen in normal control subjects. However, the PG sensitivity of Ea is restored earlier after surgery, while ME show a delayed recovery. Since the PG sensitivities correlate well with the clinical status of patients, it is suggested that such sensitivity may represent a useful test for following patients with cervical carcinoma.

Isolation and purification of fetal calf serum factor promoting mouse erythrocyte rosette formation.

This paper describes the isolation and purification of a dialyzable mouse erythrocyte rosette-promoting factor (MERF) contained in fetal calf serum (FCS). All rosette-promoting activity of FCS appears to be due to a low molecular weight, ribonuclease-sensitive material with biological activity promoting the expression of mouse erythrocyte receptors on a subset of human B lymphocytes.

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.

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.