Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Assessment of temozolomide action encapsulated in chitosan and polymer nanostructures on glioblastoma cell lines

Purpose: Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to mankind and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology. Many cancers, including gliomas, appear to be supported by cells with stem-like properties. Nanoparticles are excellent candidates to serve as delivery vectors of drugs or biologically active molecules because of their unique chemical and physical properties that result in specific transportation and deposition of such agents in specific organs and tissues.In the current study we have investigated the in vitro action of nanostructural systems (temozolomide encapsulated in chitosan and polymer nanostructures) on high-grade glioma-derived cancer stem cells (CSCs), with the intention of developing a new therapy to treat specific brain tumors with increased efficacy and minimal toxicity. In vitro cytotoxicity and apoptosis measurements indicated that the drug/vector combination facilitated the ability of the alkylating drug TMZ to alter the resistance of these cancer stem cells, suggesting a new chemotherapy strategy even for patients diagnosed with inoperable or recurrent malignant gliomas.Methods: At the National Institute for R & D of Isotopic and Molecular Technologies form Cluj Napoca were synthesized three types of nanostructures chitosan-TMZ, TMZ-chitosan-PEG (poly-ethylene glycol), TMZ-chitosan-PPG (polypropylene glycol). Three type of cell lines (Glioma-derived stem, HFL and HUVEC) were treated with the 3 types of nanostructures and the survival rate of the cells was compare to standard therapy (TMZ).Results: The results showed a reduction in the rate of survival of the tumor cells. Cell proliferation assays clearly demonstrate the differences between conventional chemotherapy (TMZ) and temozolomide encapsulated in chitosan and polymer nanostructures. Conclusion: Nanostructures like chitosan, PEG, PPG are useful as vectors for drugs transport.Despite combined therapy (surgery, radiotherapy, chemotherapy), currently median patient survival is reduced. The key to improving life expectancy could be an effective therapy targeted, customized for each case. An increasingly important role will be new methods of treatment such as immunotherapy, gene therapy or nanotherapy

Collagen scaffold and lipoaspirate fluid - Derived stem cells for the treatment of cartilage defects in a Rabbit Model

The purpose of the present study was to assess and compare the chondroregenerative properties of PLA (processed lipoaspirate) and LAF (lipoaspirate fluid) cells, in a preclinical rabbit model of knee cartilage defect. The defects were repaired by a collagen I/III scaffold and added LAF-cells, PLA-cells or no cells, upon the study group. The results showed that collagen scaffolds seeded with LAF-derived stem cells appear to have slightly better activity and outcomes when compared to PLA-cells, in terms of cartilage regeneration

Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature

Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivatives, fuels an urgent need for the precise identification of PnD and the establishment of updated consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues that are relevant for the definition/characterization of perinatal cells, starting from an understanding of the development of the human placenta, its structure, and the different cell populations that can be isolated from the different perinatal tissues. We describe where the cells are located within the placenta and their cell morphology and phenotype. We also propose nomenclature for the cell populations and derivatives discussed herein. This review is a joint effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the processing and in vitro characterization and clinical application of PnD.Austrian Science Fund (FWF) DOC 31-B26Medical University GrazUniversita Cattolica del Sacro CuorePRIN 2017 program of Italian Ministry of Research and University (MIUR) 2017RSAFK7Ministry of Health, Italy GR-2018-12366992Slovenian Research Agency - Slovenia P3-0108MRIC UL IP-0510Plan Estatal de Investigacion Cientifica y Tecnica y de InnovacionISCIII Subdireccion General de Evaluacion y Fomento de la InvestigacionMinisterio de Economia y Competitividad, Spain PI16/01642European Union (EU)European Community (EC)German Research Foundation (DFG) GE-2223/2-

Collagen scaffold and lipoaspirate fluid - Derived stem cells for the treatment of cartilage defects in a rabbit model

The purpose of the present study was to assess and compare the chondroregenerative properties of PLA (processed lipoaspirate) and LAF (lipoaspirate fluid) cells, in a preclinical rabbit model of knee cartilage defect. The defects were repaired by a collagen I/III scaffold and added LAF-cells, PLA-cells or no cells, upon the study group. The results showed that collagen scaffolds seeded with LAF-derived stem cells appear to have slightly better activity and outcomes when compared to PLA-cells, in terms of cartilage regeneratio