Epithelial ovarian cancer inherent resistance: May the pleiotropic interaction between reduced immunosurveillance and drug-resistant cells play a key role?

•Cancer cells may have inherent chemoresistance which allows an indefinite expansion.•Transformed ovarian epithelial cells may undergo an immunoediting process.•Immunoedited ovarian cancer drug-resistant cells escape first-line chemotherapy.

Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives.

Purpose: Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis.

Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives.

Background: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective;

Methods: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases;

Results: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARβ/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis;

Conclusion: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer.

Oxidative Stress during Ovarian Torsion in Pediatric and Adolescent Patients: Changing The Perspective of The Disease.

Among the different causes of gynecological acute pelvic pain, ovarian torsion represents a surgical emergency. It is a rare case in the pediatric/adolescent aged group that must be included in the differential diagnosis of any girl with abdominal pain or pelvic/abdominal mass. Current recommendations suggest that laparoscopic detorsion should be performed in order to preserve the integrity of the ovaries and fertility, although oophoropexy may be considered in case of severe necrosis.

Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner.

Purpose: Invariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic.

Management of women with epilepsy: from preconception to post-partum.

Purpose: The physiological changes during pregnancy can significantly alter antiepileptic drug (AED)'s absorption, distribution, metabolism and elimination, thus influencing their plasma concentration. Considering that the risks of using old and new AEDs during pregnancy are still debated, our aim is to review the available evidence on this topic.

Methods: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.

The pleiotropic effects of vitamin D in gynaecological and obstetric diseases: an overview on a hot topic.

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several "noncalcemic" effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer.

Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease.

Introduction: Environmental toxicants can act as endocrine disrupters on the female reproductive system. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is resistant to degradation and due to its lipophilic nature, accumulates in the fat tissue and in the food chain. Human and animal exposure to TCDD affects levels of the steroid receptors and steroid-responsive gene expression and has an impact on metabolism and serum transport of steroids.

The Role of Toll-Like Receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A New Promising Therapeutic Approach?

Perturbations in immune processes play an important role in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), a multifactorial disorder mainly characterized by severe and prolonged fatigue and tipically affecting a variety of bodily systems including the immune system. Recent reports have shown that CFS/ME is an inflammatory disorder may be associated with autoimmune responses, mainly characterized by reduced functional activity of most immune cells, including neutrophils, natural killer cells, monocytes/macrophage and dendritic cells, together with dysregulations in cytokine levels, responsible for changes in the adaptive immune system. Interactions between gut microorganisms and host immune function have been shown to contribute to aberrant inflammation in CFS/ME patients.

Toll-like receptors in Alzheimer's disease: a therapeutic perspective.

Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, loss of synapses and neurons and chronic neuroinflammation. Emerging data highlight the involvement of innate immunity, that has been shown to play opposing roles during the AD progression. Activated microglia and reactive astrocytes exert neuroprotection mediated through Aβ phagocytosis in the early stage, whereas, as the disease progresses, they fail in Aβ clearance and exert detrimental effects, including neuroinflammation and neurodegeneration.

Behavior of tumor necrosis factor-α and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages.

During endometriosis, a breakdown occurs in endometrial and peritoneal homeostasis caused by cytokine-induced cell proliferation and dysregulation of apoptosis. We studied tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1, and TNFR2 gene expression at both messenger RNA (mRNA) and protein levels in peritoneal fluid (PF) mononuclear cells (PFMCs), the percentages of these cells bearing the same markers, and soluble TNF-α (sTNF-α) values in PF of 80 women with endometriosis. We found that TNFR1 mRNA and protein levels, the percentages of TNFR1-bearing PFMCs, and sTNF-α values decreased from minimal to severe stages of the disease.

Interplay between Misplaced Müllerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis.

In the genetic regulation of Müllerian structures development, a key role is played by Hoxa and Wnt clusters, because they lead the transcription of different genes according to the different phases of the organogenesis, addressing correctly cell-to-cell interactions, allowing, finally, the physiologic morphogenesis. Accumulating evidence is suggesting that dysregulation of Wnt and/or Hox genes may affect cell migration during organogenesis and differentiation of Müllerian structures of the female reproductive tract, with possible dislocation and dissemination of primordial endometrial stem cells in ectopic regions, which have high plasticity to differentiation. We hypothesize that during postpubertal age, under the influence of different stimuli, these misplaced and quiescent ectopic endometrial cells could acquire new phenotype, biological functions, and immunogenicity.

Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis.

In endometriosis, regurgitating endometrial cells fail to undergo apoptosis and implant themselves outside the uterus, particularly in the peritoneum. We studied Fas and FasL behaviour by evaluating the percentages of mFas and mFasL-bearing mononuclear cells from peritoneal fluid, the level of Fas and FasL gene expression at both mRNA and protein levels in the same cells, and the sFas and sFasL values in peritoneal fluid of 80 endometriotic women, at four stages of disease severity. We found no variation in percentage of mFas-bearing mononuclear cells; high and unchanging levels of Fas mRNA and protein, and high and invariable sFas values.

Short communication: impairment of membrane markers on peripheral blood mononuclear cells and imbalance of cytokine secretion in the pathogenesis of multiple sclerosis active phases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In active disease, a transmigration of autoreactive T cells to myelin antigens recruited from the peripheral blood (PBMC) to the CNS occurs, and there these cells prolong their survival and contribute to the perpetuation of the inflammation. In the active local lesions of MS patients, these cells display activation and apoptosis surface markers and secrete a range of cytokines.

Imbalance of serum cytokine network in sarcoid patients: index of sarcoidosis relapse?

Background And Aim Of The Work: The follow-up of sarcoidosis is usually performed by invasive tools such as thoracic biopsy, supported by Broncho-Alveolar Lavage (BAL), Gallium-scintigraphy and Gadolinium Magnetic Resonance Imaging (Gd-MRI) to evaluate the degree of disease. Its pathogenesis can be ascribed to an accumulation of cells due to the disregulation of the immune system which involves Th1/Th2 cells as well as the soluble factors they generate. We evaluated serum cytokine and membrane marker levels (cytokine network) in sarcoid patients in order to study the correlation with the disease activity, in particular with the occurrence of sarcoidosis relapses.

Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis.

Endometriosis is a disorder characterised by presence and growth of endometrial tissue outside the uterus, primarily into the peritoneum. The peritoneal fluid (PF) of women with endometriosis undergoes a number of biological changes, including local inflammatory-reparative phenomena and peripheral blood mononuclear cells (PBMC) involvement. These activated cells as well as the endometriotic cells secrete various cytokines with pleiotropic biological activities.