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Carmignani M.,University of LAquila | Volpe A.R.,University of LAquila | Aldea M.,University of Medicine and Pharmacy, Cluj-Napoca | Soritau O.,Ion Chiricuta Comprehensive Cancer Center | And 7 more authors.
Journal of biological regulators and homeostatic agents | Year: 2014

The high malignancy of glioblastoma has been recently attributed to the presence, within the tumor, of glioblastoma stem cells (GSC) poorly responsive to chemo- and radiotherapy. Here, the potential employment of metformin and arsenic trioxide (ATO) in glioblastoma therapy is discussed focusing on their effects on GSC. Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin and ATO induce autophagy and apoptosis in glioma cells by inhibiting and stimulating the PI3K/Akt and the mitogen-activated protein kinase pathways, respectively. Both drugs promote differentiation of GSC into non-tumorigenic cells. In this regard, metformin acts via activation of the AMPK-FOXO3 axis, whereas ATO blocks the interleukin 6-induced promotion of STAT3 phosphorylation. Blood-brain barrier, easily crossed by metformin but not by ATO, undergoes important glioblastoma-induced alterations that increase its permeability, thus allowing ATO to distribute more into the glioblastoma bulk than in the normal brain parenchyma. A prompt clinical assessment of metformin and ATO in glioblastoma patients would represent a valid attempt to improve their survival.

Marincas C.,Technical University of Cluj Napoca | Butnaru A.,University of Medicine and Pharmacy, Cluj-Napoca | Soritau O.,Ion Chiricuta Comprehensive Cancer Center | Tomuleasa C.,University of Medicine and Pharmacy, Cluj-Napoca | And 2 more authors.
2011 E-Health and Bioengineering Conference, EHB 2011 | Year: 2011

The aim of this preliminary study is to establish a correlation between behavioral aspects of pluripotent stem cells and minimal exposure conditions to static magnetic field generated from a 1 Tesla MRI system of the medical operating staff (occupational exposure). To achieve this goal, cell cultures were placed in spatial positions of interest in the vicinity of the magnet according to the spatial positions of operating staff during the routine scanning activity. Static magnetic field strength and temperature were measured at these positions. The morphological changes, viability and proliferation of the stem cell cultures were investigated following exposure to the magnetic field in the study points. The study shows that there were some changes in these parameters, mainly the proliferation being greater in the static magnetic field around the magnet. © 2011 GR T Popa University.

Tomuleasa C.,Johns Hopkins University | Tomuleasa C.,Ion Chiricuta Comprehensive Cancer Center | Tomuleasa C.,Victor Babes University of Medicine and Pharmacy Timisoara | Soritau O.,Ion Chiricuta Comprehensive Cancer Center | And 15 more authors.
Journal of Gastrointestinal and Liver Diseases | Year: 2012

Background & Aims: The aim of the current study was to evaluate in vitro the anti-tumor efficacy of gold nanoparticles (GNPs) conjugated with conventional chemotherapy drugs for the treatment of liver cancer. This approach based on gold proposes a novel platform therapy with minimal toxicity and increased efficacy profiles for the destruction of hepatic cancer cells. methods. GNPs, stabilized with a monolayer of L-aspartate and additional cytostatic drugs, were successfully used as a complex tumor-targeting drug-delivery system. The drugs (doxorubicin, cisplatin, and capecitabine) were non-covalently conjugated onto the hydrophilic assemblies of GNPs-L-Aspartate nanostructure. Transmission electron microscopy was used to characterize the morphological and structural properties of these drug-metallic nanostructures. Results. The cellular proliferation rates in the presence of the anti-cancer drugs delivered by the GNPs were found to be statistically lower than those of cells exposed to the cytostatic drugs alone, indicating that GNPs facilitated an increased susceptibility of cancer cells to cisplatin, doxorubicin, and capecitabine plus ribavirin. Conclusion. This approach could offer a new chemotherapy strategy for patients diagnosed with unresectable hepatocellular carcinoma (HCC).

Tomuleasa C.,Ion Chiricuta Comprehensive Cancer Center | Kacso G.,Ion Chiricuta Comprehensive Cancer Center | Soritau O.,Ion Chiricuta Comprehensive Cancer Center | Susman S.,University of Medicine and Pharmacy, Cluj-Napoca | And 2 more authors.
Romanian Journal of Morphology and Embryology | Year: 2010

Similar to normal organs arising from normal stem cells, cancers can be viewed as organs composed of heterogeneous cellular populations arising from cancer cells with indefinite proliferation abilities. The continuous malignant progression is maintained by the proliferation of cancer stem cells and not the progeny that undergo limited proliferation before terminally differentiating. Effective therapy must eradicate malignant cells with unlimited clonogenic expansion within the primary tumor bulk. Thus, resolving both the specific cell of origin for prostate cancer and the interactions between the cells and the surrounding microenvironment within the cancer stem cell niche are crucial to appropriately define rational targets for therapeutic intervention and cure prostate cancer.

Tomuleasa C.,Ion Chiricuta Comprehensive Cancer Center | Tomuleasa C.,University of Medicine and Pharmacy, Cluj-Napoca | Soritau O.,Ion Chiricuta Comprehensive Cancer Center | Brie I.,Ion Chiricuta Comprehensive Cancer Center | And 9 more authors.
Journal of B.U.ON. | Year: 2010

Purpose: The purpose of this study was to challenge current knowledge on the potential therapeutic advantages of stem cells in radiotherapy by developing an in vitro model of the healthy tissue surrounding or replacing the widely resected tumor. After radical surgery, the start of radiotherapy is often delayed due to wound healing process, with potential loss of the opportunity for treating microscopic disease instead of macroscopic early recurrence. Hyperfractionated radiotherapy, contrary to the standard one, can extend the limits of radical surgery and shorten the gap before the onset ofpostoperative radiotherapy, with potential improvement in local control. Methods: By using both mesenchymal stem cells and pre-differentiated osteoblasts, cultured in proper pro-osteogenic media after cell irradiation, we investigated both the differences in the response to DNA damage between lineages undergoing differentiation in culture and the intensity of the mineralization process. Results: Ionizing radiation stimulated stem cell proliferation and differentiation at 0.5 Gy and 1 Gy, thus confirming in vitro the clinical results of hyperfractionated irradiation randomized trials in head and neck cancers (HNCs). Conclusion: To our knowledge, this study is the first to investigate the biophysics of low dose gamma irradiation on stem cell culture, focusing on the potential applications in radiation oncology. For advanced oral cavity and oropharyngeal cancers, as radical surgery often implies major bone resection, the use of mesenchymal stem cells as bone reconstruction vectors might shorten the onset of adjuvant hyperfractionated radiotherapy which enhances the mineralization process. As postoperative radiotherapy has recently being revisited for osteosarcoma, this scenario could impact also on bone reconstruction process in this pathology. © 2010 Zerbinis Medical Publications.

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