@article{Alexander2019, abstract = {Abstract The stromal vascular fraction (SVF) is a heterogeneous population of stem/stromal cells isolated from perivascular and extracellular matrix (ECM) of adipose tissue complex (ATC). Administration of SVF holds a strong therapeutic potential for regenerative and wound healing medicine applications aimed at functional restoration of tissues damaged by injuries or chronic diseases. SVF is commonly divided into cellular stromal vascular fraction (cSVF) and tissue stromal vascular fraction (tSVF). Cellular SVF is obtained from ATC by collagenase digestion, incubation/isolation, and pelletized by centrifugation. Enzymatic disaggregation may alter the relevant biological characteristics of adipose tissue, while providing release of complex, multiattachment of cell-to-cell and cell-to-matrix, effectively eliminating the bioactive ECM and periadventitial attachments. In many countries, the isolation of cellular elements is considered as a “more than minimal” manipulation, and is most often limited to controlled clinical trials and subject to regulatory review. Several alternative, nonenzymatic methods of adipose tissue processing have been developed to obtain via minimal mechanical manipulation an autologous tSVF product intended for delivery, reducing the procedure duration, lowering production costs, decreasing regulatory burden, and shortening the translation into the clinical setting. Ideally, these procedures might allow for the integration of harvesting and processing of adipose tissue for ease of injection, in a single procedure utilizing a nonexpanded cellular product at the point of care, while permitting intraoperative autologous cellular and tissue-based therapies. Here, we review and discuss the options, advantages, and limitations of the major strategies alternative to enzymatic processing currently developed for minimal manipulation of adipose tissue. Stem Cells Translational Medicine 2019;8:1265&1271 }, author = {Alexander, Robert W. and Trivisonno, Angelo and Baldari, Silvia and Cohen, Steven R. and Di Rocco, Giuliana and Gentile, Pietro and Magalon, Guy and Magalon, Jérémy and Miller, Randy B. and Toietta, Gabriele and Womack, Hayley}, doi = {10.1002/sctm.19-0166}, journal = {Stem Cells Translational Medicine}, month = {oct}, pages = {1265-1271}, title = {Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell‐ and Tissue‐Based Therapies: Concise Review}, url = {https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fsctm.19-0166}, volume = {8}, year = {2019} } @article{Baldari2016, abstract = {Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs), suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2). Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down.}, author = {Baldari, Silvia and di Rocco, G. and Di Rocco, Giuliana and Trivisonno, Angelo and Samengo, Daniela Maria and Pani, Giovambattista and Toietta, Gabriele}, doi = {10.5281/zenodo.813479}, journal = {International Journal of Molecular Sciences}, month = {jul}, pages = {1082}, title = {Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase}, url = {https://doi.org/10.3390/ijms17071082}, volume = {17}, year = {2016} } @article{Baldari2017, author = {Baldari, Silvia and Di Rocco, Giuliana and Piccoli, Martina and Pozzobon, Michela and Muraca, Maurizio and Toietta, Gabriele}, doi = {10.3390/ijms18102087}, journal = {International Journal of Molecular Sciences}, month = {oct}, pages = {2087}, title = {Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies}, url = {https://doi.org/10.3390/ijms18102087}, volume = {18}, year = {2017} } @article{Baldari2018, author = {Baldari, Silvia and Di Rocco, Giuliana and Pani, Giovambattista and Toietta, Gabriele}, doi = {10.1007/s00018-018-2931-8}, journal = {Cellular and Molecular Life Sciences}, month = {oct}, pages = {231-244}, title = {Stem cells under the influence of alcohol: effects of ethanol consumption on stem/progenitor cells}, url = {http://link.springer.com/content/pdf/10.1007/s00018-018-2931-8.pdf}, volume = {76}, year = {2018} } @article{Baldari2019, abstract = {High affinity copper binding to mitogen-activated protein kinase kinase 1 (MAP2K1, also known as MEK1) allosterically promotes the kinase activity of MEK1/2 on extracellular signal regulated kinases 1 and 2 (ERK1/2). Consequently, copper-dependent activation of the mitogen-activated (MAP) kinase pathway has a role in promoting tumor growth. Conversely, copper chelation may represent a possible therapeutic approach for a specific subset of tumors characterized by activating mutations in the serine/threonine protein kinase V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF), such as the V600E, occurring within the kinase domain (BRAFV600E). Tetrathiomolybdate (TM) is a specific copper chelating agent currently used for the treatment of Wilson’s disease and in preclinical studies for the management of metastatic cancers owing to its anti-angiogenic and anti-inflammatory properties. We evaluated in vitro and in vivo the effects of copper depletion achieved by pharmacological treatment with TM in human colorectal cells bearing the BRAFV600E mutation in comparison with BRAF wild type cells. We provide evidence that selective copper chelation differentially affects proliferation, survival and migration of colon cancer cells bearing the BRAFV600E mutation compared to BRAFwt acting via differential phosphorylation levels of ERK1/2. Moreover, tetrathiomolybdate treatment was also effective in reducing the clonogenic potential of colon cancer BRAFV600E cells resistant to BRAF pharmacological inhibition. In conclusion, these results support further assessment of copper chelation therapy as an adjuvant therapy for inhibiting the progression of colon cancers containing the BRAFV600E mutation.}, author = {Baldari, Silvia and Di Rocco, Giuliana and Heffern, Marie C. and Su, Timothy A. and Chang, Christopher J. and Toietta, Gabriele}, doi = {10.3390/cancers11050659}, journal = {Cancers}, month = {may}, pages = {659}, title = {Effects of Copper Chelation on BRAFV600E Positive Colon Carcinoma Cells}, url = {https://doi.org/10.3390/cancers11050659}, volume = {11}, year = {2019} } @article{Baldari2019_2, abstract = {Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the prominent causes of cancer mortality, leading to approximately 780,000 deaths per year worldwide. Down-regulation of microRNA-125b (miR-125b) is a prognostic indicator in HCC patients. Conversely, over-expression of miR-125b in HCC cells induces cell cycle arrest, inhibits proliferation, migration and invasion. Extracellular vesicles (EVs) function as intercellular messengers transferring proteins, RNAs, DNAs, carbohydrates, and lipids. Since EVs protect their cargo from degradation, delivery of therapeutic bioactive molecules, in particular miRNAs, through EVs represents an innovative avenue for cancer therapy. In this study, we evaluated a replacement strategy for the treatment of HCC via delivery of EVs secreted from human adipose tissue-derived mesenchymal stromal/medicinal signaling cells (ASCs) genetically modified with a lentiviral vector expressing miR-125b with a specific ExoMotif sequence tag to enhance the loading into extracellular vesicles. In particular, we determined that the delivery of miR-125b-loaded EVs produced in engineered ASCs specifically reduces HCC cell proliferation in vitro modulating a series of miR-125b targets, which belong to the p53 signaling pathway. This proof-of-concept study supports the development of innovative therapeutic strategies for HCC via EV-mediated miRNA delivery.}, author = {Baldari, Silvia and Di Rocco, Giuliana and Magenta, Alessandra and Picozza, Mario and Toietta, Gabriele}, doi = {10.3390/cells8121560}, journal = {Cells}, month = {dec}, pages = {1560}, title = {Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation}, url = {https://doi.org/10.3390/cells8121560}, volume = {8}, year = {2019} } @article{Baldari2020, abstract = {Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.}, author = {Baldari, Silvia and Di Rocco, Giuliana and Toietta, Gabriele}, doi = {10.3390/ijms21031069}, journal = {International Journal of Molecular Sciences}, month = {feb}, pages = {1069}, title = {Current Biomedical Use of Copper Chelation Therapy}, url = {https://doi.org/10.3390/ijms21031069}, volume = {21}, year = {2020} } @article{Baldari2021, abstract = {Endogenous acetaldehyde production from the metabolism of ingested alcohol exposes hematopoietic progenitor cells to increased genotoxic risk. To develop possible therapeutic strategies to prevent or reverse alcohol abuse effects, it would be critical to determine the temporal progression of acute ethanol toxicity on progenitor cell numbers and proliferative status. We followed the variation of the cell proliferation rate in bone marrow and spleen in response to acute ethanol intoxication in the MITO-Luc mouse, in which NF-Y-dependent cell proliferation can be assessed in vivo by non-invasive bioluminescent imaging. One week after ethanol administration, bioluminescent signals in bone marrow and spleen decreased below the level corresponding to physiological proliferation, and they progressively resumed to pre-treatment values in approximately 4 weeks. Boosting acetaldehyde catabolism by administration of an aldehyde dehydrogenase activity activator or administration of polyphenols with antioxidant activity partially restored bone marrow cells’ physiological proliferation. These results indicate that in this mouse model, bioluminescent alteration reflects the reduction of the physiological proliferation rate of bone marrow progenitor cells due to the toxic effect of aldehydes generated by alcohol oxidation. In summary, this study presents a novel view of the impact of acute alcohol intake on bone marrow cell proliferation in vivo.}, author = {Baldari, Silvia and Manni, Isabella and Di Rocco, Giuliana and Paolini, Francesca and Palermo, Belinda and Piaggio, Giulia and Toietta, Gabriele}, doi = {10.3390/cancers13194999}, journal = {Cancers}, month = {oct}, pages = {4999}, title = {Reduction of Cell Proliferation by Acute C2H6O Exposure}, url = {https://doi.org/10.3390/cancers13194999}, volume = {13}, year = {2021} } @article{Contadini2019, abstract = {AbstractCentrosomal p53 has been described for three decades but its role is still unclear. We previously reported that, in proliferating human cells, p53 transiently moves to centrosomes at each mitosis. Such p53 mitotic centrosome localization (p53-MCL) occurs independently from DNA damage but requires ATM-mediated p53Ser15 phosphorylation (p53Ser15P) on discrete cytoplasmic p53 foci that, through MT dynamics, move to centrosomes during the mitotic spindle formation. Here, we show that inhibition of p53-MCL, obtained by p53 depletion or selective impairment of p53 centrosomal localization, induces centrosome fragmentation in human nontransformed cells. In contrast, tumor cells or mouse cells tolerate p53 depletion, as expected, and p53-MCL inhibition. Such tumor- and species-specific behavior of centrosomal p53 resembles that of the recently identified sensor of centrosome-loss, whose activation triggers the mitotic surveillance pathway in human nontransformed cells but not in tumor cells or mouse cells. The mitotic surveillance pathway prevents the growth of human cells with increased chance of making mitotic errors and accumulating numeral chromosome defects. Thus, we evaluated whether p53-MCL could work as a centrosome-loss sensor and contribute to the activation of the mitotic surveillance pathway. We provide evidence that centrosome-loss triggered by PLK4 inhibition makes p53 orphan of its mitotic dock and promotes accumulation of discrete p53Ser15P foci. These p53 foci are required for the recruitment of 53BP1, a key effector of the mitotic surveillance pathway. Consistently, cells from patients with constitutive impairment of p53-MCL, such as ATM- and PCNT-mutant carriers, accumulate numeral chromosome defects. These findings indicate that, in nontransformed human cells, centrosomal p53 contributes to safeguard genome integrity by working as sensor for the mitotic surveillance pathway.}, author = {Contadini, Claudia and Monteonofrio, Laura and Virdia, Ilaria and Prodosmo, Andrea and Valente, Davide and Chessa, Luciana and Musio, Antonio and Fava, Luca L. and Rinaldo, Cinzia and Di Rocco, Giuliana and Soddu, Silvia}, doi = {10.1038/s41419-019-2076-1}, journal = {Cell Death and Disease}, month = {nov}, title = {p53 mitotic centrosome localization preserves centrosome integrity and works as sensor for the mitotic surveillance pathway}, url = {https://oadoi.org/10.1038/s41419-019-2076-1}, volume = {10}, year = {2019} } @article{Di Rocco2016, abstract = {Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate. Immunohistochemical detection in brain sections of cells positive for both luciferase and the microglial marker allograft inflammatory factor 1 suggests proliferation of microglial cells. In addition, we demonstrated that brain induction of bioluminescence was altered by pharmacological displacement of bilirubin from its albumin binding sites and by modulation of the blood–brain barrier permeability, all pivotal factors in the development of bilirubin-induced neurologic dysfunction. We also determined that treatment with minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, or administration of bevacizumab, an anti-vascular endothelial growth factor antibody, blunts bilirubin-induced bioluminescence. Overall the study supports the use of the MITO-Luc mouse as a valuable tool for the rapid response monitoring of drugs aiming at preventing acute bilirubin-induced neurological dysfunction. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down.}, author = {Di Rocco, Giuliana and Manni, Isabella and Fusco, Salvatore and Barbati, Saviana Antonella and Leone, Lucia and Carapella, Carmine Maria and Grassi, Claudio and Piaggio, Giulia and Toietta, Gabriele}, doi = {10.3390/ijms18010050}, journal = {Zenodo}, month = {jan}, pages = {50}, title = {Monitoring the response of hyperbilirubinemia in the mouse brain by In vivo bioluminescence imaging}, url = {https://doi.org/10.5281/zenodo.813877}, volume = {18}, year = {2016} } @article{Di Rocco2017, abstract = {Abstract: Extracellular vesicles (EVs), including exosomes and microvesicles, are critical mediators of cellto- cell communication in tissue homeostasis and repair, both in physiological and pathological conditions. Recently, progress has been achieved in their use in regenerative medicine as transfer agents for active biomolecules. Specifically, EVs are natural carriers of microRNAs (miRNAs), protecting their cargo from plasma ribonucleases and delivering their content to recipient cells. Expression of miRNAs is dysregulated in virtually all forms of cancer. Therefore, EVs-mediated miRNA delivery may represent a valuable tool for cancer therapeutic intervention, aiming at restoring cancer miRNAs expression to normal levels. MicroRNAs may act both as tumor suppressors or oncogenes, consequently different alternative approaches for regulating miRNA expression in tumor tissues have been developed. Here, we review the various strategies for miRNA loading into EVs and highlight studies of EVs-mediated miRNA delivery which have been employed for cancer treatment, both in vitro and in vivo . Collectively, these data support the use of EVs in miRNAs/miRNAs antagonist transfer for cancer therapy, but challenges related to EV biology have yet to be further addressed before safe clinical translation.}, author = {Di Rocco, Giuliana and Baldari, Silvia and Toietta, Gabriele}, doi = {10.21037/tcr.2017.09.29}, journal = {Translational Cancer Research}, month = {oct}, pages = {S1321-S1330}, title = {Exosomes and other extracellular vesicles-mediated microRNA delivery for cancer therapy}, url = {https://zenodo.org/record/1039229/files/article.pdf}, volume = {6}, year = {2017} } @article{Di Rocco2018, author = {Di Rocco, Giuliana and Rocco, G. D. and Baldari, Silvia and Gentile, Antonietta and Capogrossi, Maurizio C. and Toietta, Gabriele}, doi = {10.1186/s13287-018-0986-y}, journal = {Stem Cell Research and Therapy}, month = {sep}, title = {Protein disulfide isomerase as a prosurvival factor in cell therapy for muscular and vascular diseases}, url = {http://link.springer.com/content/pdf/10.1186/s13287-018-0986-y.pdf}, volume = {9}, year = {2018} } @article{Di Segni2022, abstract = {Abstract Homeodomain-interacting protein kinase 2 (HIPK2) is an evolutionary conserved kinase that has gained attention as a fine tuner of multiple signaling pathways, among which those commonly altered in colorectal cancer. The aim of this study was to evaluate the relationship of HIPK2 expression with progression markers and mutational pattern and gain insights into the contribution of HIPK2 activity in colorectal cancer. We evaluated a retrospective cohort of colorectal cancer samples by IHC for HIPK2 expression and by next-generation sequencing (NGS) for the detection of mutations of cancer associated genes. We show that the percentage of HIPK2-positive cells increases with tumor progression, significantly correlates with tumor–node–metastasis (TNM) staging and associates with a worse outcome. In addition, we observed that high HIPK2 expression significantly associates with KRAS mutations but not with other cancer-related genes. Functional characterization of the link between HIPK2 and KRAS show that activation of the RAS pathway either due to KRAS mutation or via upstream receptor stimulation, increases HIPK2 expression at the protein level. Of note, HIPK2 physically participates in the active RAS complex while HIPK2 depletion impairs ERK phosphorylation and the growth of tumors derived from KRAS mutated colorectal cancer cells. Overall, this study identifies HIPK2 as a prognostic biomarker candidate in patients with colorectal cancer and underscores a previously unknown functional link between HIPK2 and the KRAS signaling pathway. Implications: Our data indicate HIPK2 as a new player in the complex picture of the KRAS signaling network, providing rationales for future clinical studies and new treatment strategies for KRAS mutated colorectal cancer. }, author = {Di Segni, Micol and Virdia, Ilaria and Verdina, Alessandra and Amoreo, Carla Azzurra and Baldari, Silvia and Toietta, Gabriele and Diodoro, Maria Grazia and Mottolese, Marcella and Sperduti, Isabella and Moretti, Fabiola and Buglioni, Simonetta and Soddu, Silvia and Di Rocco, Giuliana}, doi = {10.1158/1541-7786.mcr-21-0628}, journal = {Molecular Cancer Research}, month = {jan}, pages = {686-698}, title = {HIPK2 cooperates with KRAS signaling and associates with colorectal cancer progression}, url = {https://aacrjournals.org/mcr/article-pdf/20/5/686/3117547/686.pdf}, volume = {20}, year = {2022} } @article{Dinami2020, abstract = {Abstract Background Colorectal cancer is one of most common tumors in developed countries and, despite improvements in treatment and diagnosis, mortality rate of patients remains high, evidencing the urgent need of novel biomarkers to properly identify colorectal cancer high-risk patients that would benefit of specific treatments. Recent works have demonstrated that the telomeric protein TRF2 is over-expressed in colorectal cancer and it promotes tumor formation and progression through extra-telomeric functions. Moreover, we and other groups evidenced, both in vitro on established cell lines and in vivo on tumor bearing mice, that TRF2 regulates the vascularization mediated by VEGF-A. In the present paper, our data evidence a tight correlation between TRF2 and VEGF-A with prognostic relevance in colorectal cancer patients. Methods For this study we sampled 185 colorectal cancer patients surgically treated and diagnosed at the Regina Elena National Cancer Institute of Rome and investigated the association between the survival outcome and the levels of VEGF-A and TRF2. Results Tissue microarray immunohistochemical analyses revealed that TRF2 positively correlates with VEGF-A expression in our cohort of patients. Moreover, analysis of patients’ survival, confirmed in a larger dataset of patients from TCGA, demonstrated that co-expression of TRF2 and VEGF-A correlate with a poor clinical outcome in stage I-III colorectal cancer patients, regardless the mutational state of driver oncogenes. Conclusions Our results permitted to identify the positive correlation between high levels of TRF2 and VEGF-A as a novel prognostic biomarker for identifying the subset of high-risk colorectal cancer patients that could benefit of specific therapeutic regimens. }, author = {Dinami, Roberto and Porru, Manuela and Amoreo, Carla Azzurra and Sperduti, Isabella and Mottolese, Marcella and Buglioni, Simonetta and Marinelli, Daniele and Maugeri-Saccà, Marcello and Sacconi, Andrea and Blandino, Giovanni and Leonetti, Carlo and Di Rocco, Giuliana and Verdina, Alessandra and Spinella, Francesca and Fiorentino, Francesco and Ciliberto, Gennaro and Biroccio, Annamaria and Zizza, Pasquale}, doi = {10.1186/s13046-020-01612-z}, journal = {Journal of Experimental and Clinical Cancer Research}, month = {jun}, title = {TRF2 and VEGF-A: an unknown relationship with prognostic impact on survival of colorectal cancer patients}, url = {https://doi.org/10.1186/s13046-020-01612-z}, volume = {39}, year = {2020} } @article{D’Eliseo2016, author = {D’Eliseo, Donatella and Di Rocco, Giuliana and Loria, Rossella and Soddu, Silvia and Santoni, Angela and Velotti, Francesca}, doi = {10.1186/s13046-016-0302-6}, journal = {Journal of Experimental and Clinical Cancer Research}, month = {feb}, title = {Epitelial-to-mesenchimal transition and invasion are upmodulated by tumor-expressed granzyme B and inhibited by docosahexaenoic acid in human colorectal cancer cells}, url = {http://dx.doi.org/10.1186/s13046-016-0302-6}, volume = {35}, year = {2016} } @article{Gatti2020, abstract = {HIPK2 is a DYRK-like kinase involved in cellular stress response pathways, development, and cell division. Two alternative splice variants of HIPK2, HIPK2-FL and HIPK2-Δe8, have been previously identified as having different protein stability but similar functional activity in the stress response. Here, we describe one additional HIPK2 splice variant with a distinct subcellular distribution and functional activity in cytokinesis. This novel splice variant lacks the last two exons and retains intron13 with a stop codon after 89 bp of the intron, generating a short isoform, HIPK2-S, that is detectable by 2D Western blots. RT-PCR analyses of tissue arrays and tumor samples show that HIPK2-FL and HIPK2-S are expressed in normal human tissues in a tissue-dependent manner and differentially expressed in human colorectal and pancreatic cancers. Gain- and loss-of-function experiments showed that in contrast to HIPK2-FL, HIPK2-S has a diffuse, non-speckled distribution and is not involved in the DNA damage response. Rather, we found that HIPK2-S, but not HIPK2-FL, localizes at the intercellular bridge, where it phosphorylates histone H2B and spastin, both required for faithful cell division. Altogether, these data show that distinct human HIPK2 splice variants are involved in distinct HIPK2-regulated functions like stress response and cytokinesis.}, author = {Gatti, Veronica and Ferrara, Manuela and Virdia, Ilaria and Matteoni, Silvia and Monteonofrio, Laura and di Martino, Simona and Diodoro, Maria Grazia and Di Rocco, Giuliana and Rinaldo, Cinzia and Soddu, Silvia}, doi = {10.3390/cells9020484}, journal = {Cells}, month = {feb}, pages = {484}, title = {An Alternative Splice Variant of HIPK2 with Intron Retention Contributes to Cytokinesis}, url = {https://doi.org/10.3390/cells9020484}, volume = {9}, year = {2020} } @article{Mariani2016, abstract = {The sirtuin family comprises seven NAD+-dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral adipose-derived stem cells of obese patients.}, author = {Mariani, Stefania and Di Rocco, Giuliana and Russo, Matteo Antonio and Petrangeli, Elisa and Toietta, Gabriele and Salvatori, Luisa and , }, doi = {10.1007/s12020-016-1170-8}, journal = {Endocrine}, month = {nov}, title = {Sirtuins 1–7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia}, url = {https://oadoi.org/10.1007/s12020-016-1170-8}, year = {2016} } @article{Trivisonno2020, abstract = {Abstract Respiratory tract fistulas (or fistulae) are abnormal communications between the respiratory system and the digestive tract or the adjacent organs. The origin can be congenital or, more frequently, iatrogenic and the clinical presentation is heterogeneous. Respiratory tract fistulas can lead to severely reduced health-related quality of life and short survival. Therapy mainly relies on endoscopic surgical interventions but patients often require prolonged hospitalization and may develop complications. Therefore, more conservative regenerative medicine approaches, mainly based on lipotransfer, have also been investigated. Adipose tissue can be delivered either as unprocessed tissue, or after enzymatic treatment to derive the cellular stromal vascular fraction. In the current narrative review, we provide an overview of the main tissue/cell-based clinical studies for the management of various types of respiratory tract fistulas or injuries. Clinical experience is limited, as most of the studies were performed on a small number of patients. Albeit a conclusive proof of efficacy cannot be drawn, the reviewed studies suggest that grafting of adipose tissue-derived material may represent a minimally invasive and conservative treatment option, alternative to more aggressive surgical procedures. Knowledge on safety and tolerability acquired in prior studies can lead to the design of future, larger trials that may exploit innovative procedures for tissue processing to further improve the clinical outcome.}, author = {Trivisonno, Angelo and Nachira, Dania and Boškoski, Ivo and Porziella, Venanzio and Di Rocco, Giuliana and Baldari, Silvia and Toietta, Gabriele}, doi = {10.1186/s13287-020-01968-1}, journal = {Stem Cell Research and Therapy}, month = {oct}, title = {Regenerative medicine approaches for the management of respiratory tract fistulas}, url = {https://doi.org/10.1186/s13287-020-01968-1}, volume = {11}, year = {2020} } @article{Verdina2017, author = {Verdina, Alessandra and Di Rocco, Giuliana and Virdia, Ilaria and Monteonofrio, Laura and Gatti, Veronica and Policicchio, Eleonora and Bruselles, Alessandro and Tartaglia, Marco and Soddu, Silvia}, doi = {10.18632/oncotarget.14421}, journal = {Oncotarget}, month = {jan}, pages = {16744-16754}, title = {HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation}, url = {https://doi.org/10.18632/oncotarget.14421}, volume = {8}, year = {2017} } @article{Verdina2020, author = {Verdina, Alessandra and Di Segni, Micol and Amoreo, Carla and Sperduti, Isabella and Buglioni, Simonetta and Mottolese, Marcella and Di Rocco, Giuliana and Soddu, Silvia}, doi = {10.3892/or.2020.7912}, journal = {Oncology Reports}, month = {dec}, pages = {899-910}, title = {HIPK2 is a potential predictive marker of a favorable response for adjuvant chemotherapy in stage II colorectal cancer}, url = {https://oadoi.org/10.3892/or.2020.7912}, volume = {45}, year = {2020} }