Search results for " research."
showing 10 items of 13407 documents
The Role of Osteoprotegerin and Its Ligands in Vascular Function
2019
International audience; The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular comp…
Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies
2017
Thymoquinone (TQ), the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological pro…
Pharmacogenetics of Metabolic Genes of Anthracyclines in Acute Myeloid Leukemia.
2018
Background Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. Methods A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity. Results Polymorphisms in the main enzymes of anthracyclines metabolism (CBR, AKR,…
Abstract 882: The anti-claudin 6 antibody, IMAB027, induces antibody-dependent cellular and complement-dependent cytotoxicity in claudin 6-expressing…
2018
Abstract Background Claudin 6 (CLDN6) is a tight junction membrane protein whose expression in normal tissue is confined to embryonic cells, but aberrantly expressed in various human cancer types, including some with a high medical need (eg, ovarian and uterine cancers). This tumor-specific expression in adult organs makes CLDN6 an attractive drug target; as such, IMAB027, an anti-CLDN6 monoclonal antibody (mAb), was developed. This report describes the preclinical characteristics of IMAB027. Methods IMAB027 was generated by hybridoma technology; the discovery process was set up so that mAbs that were good binders as well as inducers of the immune effector mechanisms of antibody-dependent c…
Harnessing Tumor Mutations for Truly Individualized Cancer Vaccines
2019
T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex–bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell–mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor. Knowledge of an individual's cancer mutanome (the entirety of cancer mutations) allows harnessing this enormous tumor cell–specific repertoire of highly immunogenic antigens for individualized cancer vaccines. This review outlines the preclinical and clinical state of individualized cancer vaccine development and t…
DNA demethylation caused By 5-Aza-2'-Deoxycytidine induces mitotic alterations and aneuploidy
2016
Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduc…
Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?
2016
// Daniele Fanale 1, * , Valeria Amodeo 1, * , Viviana Bazan 1, * , Lavinia Insalaco 1 , Lorena Incorvaia 1 , Nadia Barraco 1 , Marta Castiglia 1 , Sergio Rizzo 1 , Daniele Santini 2 , Antonio Giordano 3 , Sergio Castorina 4, 5, # , Antonio Russo 1, # 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 University Campus Bio-Medico, Department of Medical Oncology, Rome, Italy 3 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA 4 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 5 Department of Biomedic…
Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma
2020
Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of …
MicroRNA targeting by quercetin in cancer treatment and chemoprotection
2019
A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer properties due to their proven antioxidant, anti-inflammatory, and anti-proliferative effects. Available experimental studies indicate that quercetin could modulate multiple cancer-relevant miRNAs including let-7, miR-21, miR-146a and miR-155, thereby inhibiting cancer initiation and development. This paper reviews the data supporting the use of quercetin for miRNA-mediated chem…
Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols.
2017
Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological production of nitric oxide reduces oxidative stress and inflammation, however, the precise mechanism of “antioxidant” effect of nitric oxide is not clear. In this work we tested the hypothesis that physiological levels of nitric oxide diminish mitochondrial superoxide production without inhibition of mitochondrial respiration. In order to test this hypothesis we analyzed effect of low p…