MiRNAs as Regulators of Immune Cells in the Tumor Microenvironment of Ovarian Cancer.

Ovarian cancer is one of the leading causes of cancer deaths among women. There is an ongoing need to develop new biomarkers and targeted therapies to improve patient outcomes. One of the most critical research areas in ovarian cancer is identifying tumor microenvironment (TME) functions.

High-Grade Serous Ovarian Cancer-A Risk Factor Puzzle and Screening Fugitive.

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients ( germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy.

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer-The Possibility or the Necessity?

High-grade serous tubo-ovarian cancer (HGSTOC) is the most lethal tumor of the female genital tract. The foregoing therapy consists of cytoreduction followed by standard platinum/taxane chemotherapy; alternatively, for primary unresectable tumors, neo-adjuvant platinum/taxane chemotherapy followed by delayed interval cytoreduction. In patients with suboptimal surgery or advanced disease, different forms of targeted therapy have been accepted or tested in clinical trials.

Prediction of Chemoresistance-How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is one of the most lethal tumors generally and the most fatal cancer of the female genital tract. The approved standard therapy consists of surgical cytoreduction and platinum/taxane-based chemotherapy, and of targeted therapy in selected patients. The main therapeutic problem is chemoresistance of recurrent and metastatic HGSOC tumors which results in low survival in the group of FIGO III/IV.

"DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.

Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing.

Endometriosis Stem Cells as a Possible Main Target for Carcinogenesis of Endometriosis-Associated Ovarian Cancer (EAOC).

Endometriosis is a serious recurrent disease impairing the quality of life and fertility, and being a risk for some histologic types of ovarian cancer defined as endometriosis-associated ovarian cancers (EAOC). The presence of stem cells in the endometriotic foci could account for the proliferative, migrative and angiogenic activity of the lesions. Their phenotype and sources have been described.

The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer.

Ovarian cancer (OC) is one of the most common cancers threatening women's lives around the world. Epithelial ovarian tumors represent the most common ovarian neoplasms. Most OC patients are diagnosed at the advanced stage, and there is an urgent need to identify novel biomarkers of the disease.

Cancer Stem Cells in Ovarian Cancer-A Source of Tumor Success and a Challenging Target for Novel Therapies.

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells.

Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients.

Viral and bacterial infections are detected in epithelial ovarian cancer (EOC) tissues. Since the fallopian tubes are often affected by pelvic inflammatory disease (PID) and the majority of serous EOCs appear to originate from dysplastic lesions in the distal tube, it is relevant to consider the potential role that infectious agents may play in ovarian carcinogenesis. We sought to analyze the prevalence of human papillomavirus (HPV) and cytomegalovirus (CMV) in EOC tissue and fallopian tube specimens obtained at tumor resection.

Pulmonary torsion as an atypical complication of congenital esophageal atresia repair-a case report and review of literature.

Pulmonary torsion is a severe, life-threatening event, rarely occurring in children. We present a case of atypical postoperative complication of esophageal atresia repair in the form of pulmonary torsion comprising the middle lobe of the right lung. Clinical deterioration in the face of normal arterial blood gases should rise a high index of suspicion for pulmonary torsion.

Mitochondrial dysfunction in cancer.

Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS) system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS) generation.

Long-term follow-up of children with congenital diaphragmatic hernia--observations from a single institution.

Introduction: Congenital diaphragmatic hernia (CDH) is a complex malformation. The majority of children after CDH repair lead normal life, with good exercise tolerance. However, in some patients, long-term sequelae are observed, resulting from the primary defect and implemented treatment.

Targeting NF-κB and HIF-1 pathways for the treatment of cancer: part I.

The process of chronic inflammation is a common link which connects different kinds of environmental pollutants and infections with tumorigenesis. Transcription factor NF-κB is a common final target for many inflammatory and cell proliferation pathways, independent of the source of stimuli (e.g.

Targeting NF-κB and HIF-1 pathways for the treatment of cancer: part II.

Hypoxia that originates from disturbed growth of solid tumors initiates a cascade of intracellular events engaging hypoxia-inducible factors, HIF-1 and HIF-2. Overexpression of HIF has been confirmed in solid tumors and was unfortunately accompanied with chemo- and radioresistance observed in many patients. Multiple cellular pathways resulting in HIF activation could be successfully inhibited by use of different kinds of drugs (e.

The role of T-regulatory cells in pregnancy and cancer.

The acceptance of paternally-derived alloantigens during pregnancy and escape from host immunosurveillance by cancer are based on similar immunological mechanisms. Among them both natural and peripherally-induced T CD4+ CD25+ Foxp3+ and Tr1 regulatory cells (Tregs) play important role. Interactions of Tregs with other immunocytes including dendritic cells, mechanisms of Tregs recruitment and their suppressive properties in cancer and pregnancy have been presented in this paper.

The characterization and role of regulatory T cells in immune reactions.

Regulatory T cells (Tregs) having CD4+ CD25+ Foxp3+ or CD4+ IL-10+ (Tr1) phenotype and capable of inducing anergy towards self- and alloantigens play an important role in autoimmunity, as well as in tolerance of allografts, pregnancy and cancer. Both thymus-derived T CD4+ CD25+ Foxp3+ natural cells and peripherally-induced T CD4+ CD25+ Foxp3+ cells prevent migration of effector immunocytes to target organs and inhibit their cooperation with antigen-presenting cells. The suppressive function of CD4+ CD25+ Foxp3+ Tregs depends on interactions between stimulatory (IL-2, CTLA-4) and inhibitory (GITR, CD28) signals, on stimulation of indoleamine 2,3-dioxygenase (IDO) activity in dendritic cells via CD80/CD86 molecules, and finally on cell-cell inhibition of effector cells by membrane-bound TGF-beta.

Fetal rejection: infertility and immunity.

Defective reaction toward fetal alloantigens could result in both recurrent spontaneous abortions (RSAs) and recurrent early pregnancy failures (REPFs), the latter existing in couples with unexplained infertility and multiple failures of implantation after in vitro fertilization embryo transfer. Immunological mechanisms leading to RSA and REPF seem to be different, although both syndromes probably have a genetic background that has not been identified so far. Despite the fact that antiphospholipid syndrome is a well-established cause of repeated pregnancy loss, the role of different autoantibodies existing in RSA and REPF patients needs to be elucidated.

Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism?

There are still controversies concerning the role of immunological mechanisms engaged both in recurrent abortions (RA) and pre-eclampsia (PE). According to some opinions, recurrent miscarriage is comparable to organ-specific autoimmune disease. Analysis of immune reactions shows that graft rejection shares many similar mechanisms with RA and PE.

Cancer and pregnancy share similar mechanisms of immunological escape.

Background: Despite the fact that trophoblasts and cancer are both immunogenic, they are able to escape from host immunosurveillance, and the precise mechanisms involved in this process are surprisingly similar in both situations.

Methods: A literature review of studies on immunological changes occurring during normal pregnancy and cancer was performed.

Results: Loss or downregulation of classical HLA antigens as well as the presence of non-classical HLA-G molecules, a Th2 cytokine activity shift, secretion of immunosuppressive factors and blocking antibodies and finally induction of apoptosis in immunocytes seem to be the most effective mechanisms of immunological escape in pregnancy and cancer.

Th1/Th2 cytokines balance--yin and yang of reproductive immunology.

For years conception of Th2 overbalance during pregnancy has been a paradigm for immunology of reproduction, while Th1 activity has been presented as unwanted component. Studies concerning Th1/Th2 balance in physiological and complicated pregnancy have been reviewed. Th1 activity during early peri-implantation period, premature and term labour not only accompanies but even predominates over Th2 activity.

'In vitro' cytokine secretion by peripheral blood and decidual lymphocytes during the third trimester of normal pregnancy.

If the 'Th2 phenomenon' is dependent on trophoblastic antigens and cytokines, the profile of cytokines secreted by decidual lymphocytes (DL) should indicate stronger Th2 shift than that of peripheral blood lymphocytes (PBL). We studied spontaneous and mitogen-stimulated 'in vitro' cytokine secretion of cultured lymphocytes isolated from peripheral blood (n = 21) and decidua (n = 11) of third trimester healthy pregnant women not being in labor. The ELISA method was used for estimation of IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma and TGF-beta.

Expression of intercellular adhesion molecule-1 on the surface of peripheral blood and decidual lymphocytes of women with pregnancy-induced hypertension.

Objective: If overexpression of intercellular adhesion molecule-1 (CD54) on lymphocytes exists it could have important implications for the pathophysiology of pregnancy-induced hypertension (PIH).

Study Design: CD54 "in vitro" expression (described as (%) of CD54+cells and CD54 mean fluorescence intensity, MFI) on the peripheral blood and decidual lymphocytes of pregnant with pre-eclampsia (PE) (n=16), transient hypertension (TH) (n=12), and controls (n=9).

Results: The percent (%) of CD54+peripheral blood lymphocytes, CD54 MFI on them and CD54 MFI on decidual lymphocytes were increased especially in PE.