PTEN is one of the most frequently inactivated tumor suppressor genes in cancer. Loss or variation in PTEN gene/protein levels is commonly observed in a broad spectrum of human cancers, while germline PTEN mutations cause inherited syndromes that lead to increased risk of tumors. PTEN restrains tumorigenesis through different mechanisms ranging from phosphatase-dependent and independent activities, subcellular localization and protein interaction, modulating a broad array of cellular functions including growth, proliferation, survival, DNA repair, and cell motility. The main target of PTEN phosphatase activity is one of the most significant cell growth and pro-survival signaling pathway in cancer: PI3K/AKT/mTOR. Several shreds of evidence shed light on the critical role of PTEN in normal and cancer stem cells (CSCs) homeostasis, with its loss fostering the CSC compartment in both solid and hematologic malignancies. CSCs are responsible for tumor propagation, metastatic spread, resistance to therapy, and relapse. Thus, understanding how alterations of PTEN levels affect CSC hallmarks could be crucial for the development of successful therapeutic approaches. Here, we discuss the most significant findings on PTEN-mediated control of CSC state. We aim to unravel the role of PTEN in the regulation of key mechanisms specific for CSCs, such as self-renewal, quiescence/cell cycle, Epithelial-to-Mesenchymal-Transition (EMT), with a particular focus on PTEN-based therapy resistance mechanisms and their exploitation for novel therapeutic approaches in cancer treatment.
Summary New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials.
Recent experiments have shown that cells with different genetic mutations can give rise to cancer transformation, both in vitro and in vivo, supported by the crosstalk between cancer cells and stroma. The stroma and the complex set of involved cells make up the tumor microenvironment that supports the engraftment of metastatic cells. In fact, environmental factors support colorectal cancer arise by formation and maintenance of cancer stem cells (CSCs). In this review, we discuss interactions between CSCs and their microenvironment that can provide better therapeutic opportunities in the metastatic cancer.
During home pizza delivery in cardboard boxes uncontrolled heat and mass transfer processes occur. This work aimed to evaluate how the textural and sensory properties change from the moment the pizza is taken out of the oven and the moment of its consumption at home. Such properties were also assessed for a novel takeaway pizza service involving pizza baking, freezing, packing, delivery and reheating at home to save leavened dough balls unused at the end of everyday working activity. Panellists preferred freshly baked pizza, but frozen pizza was more preferred over all pizzas kept in cardboard boxes for 10-30 min. The cradle-to-grave carbon footprint and cost of frozen pizza were finally assessed to show how such a food product, that would have been wasted, might be profitably converted into a high-quality alternative takeaway pizza service.
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