Gene Expression Signature of Acquired Chemoresistance in Neuroblastoma Cells

Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. Patients with relapsed disease have a poor prognosis despite intense treatment. In the present study, we aimed to identify chemoresistance gene expression signatures in vincristine resistant neuroblastoma cells. We found that vincristine-resistant neuroblastoma cells formed larger clones and survived under reduced serum conditions as compared with non-resistant parental cells. To identify the possible mechanisms underlying vincristine resistance in neuroblastoma cells, we investigated the expression profiles of genes known to be involved in cancer drug resistance. This specific gene expression patterns could predict the behavior of a tumor in response to chemotherapy and for predicting the prognosis of high-risk neuroblastoma patients. Our signature could help chemoresistant neuroblastoma patients in avoiding useless and harmful chemotherapy cycles

Mitotic spindle as therapeutic target for tetraploid cancer cells

Tetraploidy constitutes a genomically metastable state that drives oncogenesis by leading aneuploidy. Tetraploid sub-population is frequently found in pre-neoplastic lesions. This particular population is relatively more resistant against DNA damaging agents and in consequence, it is important to selectively target tetraploid cancer cells. Here, we listed all the studies that targeted preferentially tetraploid tumors cells focusing on mitosis machinery, essentially the spindle pole apparatus and the spindle assembly checkpoint pathways

Methods Employed in Cytofluorometric Assessment of Eryptosis, the Suicidal Erythrocyte Death

Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins. Eryptosis is characterized by cell membrane scrambling with phosphatidylserine exposure to the erythrocyte surface. Triggers of eryptosis include oxidative stress, hyperosmotic shock, and energy depletion. Signalling involved in the regulation of eryptosis includes Ca2+ entry, ceramide, caspases, calpain, p38 kinase, protein kinase C, Janus-activated kinase 3, casein kinase 1α, cyclin-dependent kinase 4, AMP-activated kinase, p21-activated kinase 2, cGMP-dependent protein kinase, mitogen- and stress-activated kinase MSK1/2, and ill-defined tyrosine kinases. Inhibitors of eryptosis may prevent anaemia in clinical conditions associated with enhanced eryptosis and stimulators of eryptosis may favourably influence the clinical course of malaria. Additional experimentation is required to uncover further clinical conditions with enhanced eryptosis, as well as further signalling pathways, further stimulators, and further inhibitors of eryptosis. Thus, a detailed description of the methods employed in the analysis of eryptosis may help those, who enter this exciting research area. The present synopsis describes the experimental procedures required for the analysis of phosphatidylserine exposure at the cell surface with annexin-V, cell volume with forward scatter, cytosolic Ca2+ activity ([Ca2+]) with Fluo3, oxidative stress with 2′,7′-dichlorodihydrofuorescein diacetate (DCFDA), glutathione (GSH) with mercury orange 1(4-chloromercuryphenyl-azo-2-naphthol), lipid peroxidation with BODIPY 581/591 C11 fluorescence, and ceramide abundance with specific antibodies. The contribution of kinases and caspases is defined with the use of the respective inhibitors. It is hoped that the present detailed description of materials and methods required for the analysis of eryptosis encourages further scientists to enter this highly relevant research area

Analgesic, Anti-Inflammatory and Anticancer Activities of Extra Virgin Olive Oil

Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway