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| 1 | Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis显示文摘Hepatitis B virus(HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma(HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNAinto the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis. | Mirko Tarocchi Simone Polvani Giada Marroncini Andrea Galli | 2014 | World Journal of Gastroenterology2014，20，33： | 35 |
| 2 | Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer显示文摘Pancreatic ductal adenocarcinoma(PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks(sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ(PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stressassociated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients. | Simone Polvani Mirko Tarocchi Sara Tempesti Lapo Bencini Andrea Galli | 2016 | World Journal of Gastroenterology2016，22，8： | 17 |
| 3 | Nuclear receptors and pathogenesis of pancreatic cancer显示文摘Pancreatic ductal adenocarcinoma(PDAC)is a devastating disease with a median overall survival time of5 mo and the five years survival less than 5%,a rate essentially unchanged over the course of the years.A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease.However,due to the its subtle nature and concurring events PDAC cure remains elusive.Nuclear receptors(NR)are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism,to growth and development.Given the nature of their ligands,NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases.There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages;nonetheless many aspects of their role are not fully understood.The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors,retinoic acid receptors,retinoid X receptor,androgen receptor,estrogen receptors and the orphan NR Nur,chicken ovalbumin upstream promoter transcription factorⅡand the liver receptor homologue-1 receptor to PDAC development,connections that could lead to the identification of novel therapies for this disease. | Simone Polvani Mirko Tarocchi Sara Tempesti Andrea Galli | 2014 | World Journal of Gastroenterology2014，20，34： | 12 |
| 4 | Chemotherapy for hepatocellular carcinoma:The present and the future显示文摘Hepatocellular carcinoma(HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it's still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatinand gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC. | Marco Le Grazie Maria Rosa Biagini Mirko Tarocchi Simone Polvani Andrea Galli | 2017 | World Journal of Hepatology2017，9，21： | 11 |
| 5 | Telomerase activity: An attractive target for cancer therapeutics显示文摘Telomeres are non-coding tandem repeats of 1000-2000 TTAGGG nucleotide DNA sequences on the 3' termini of human chromosomes where they serve as protective 'caps' from degradation and loss of genes. The 'cap' at the end of chromosome required to protect its integrity is a 150-200 nucleotide-long single stranded G-rich 3' overhang that forms two higher order structures, a T-loop with Sheltering complex, or a G-quadruplex complex. Telomerase is a human ribonucleoprotein reverse transcriptase that continually added single stranded TTAGGG DNA sequences onto the single strand 3' of telomere in the 5' to 3' direction. Telomerase activity is detected in male germ line cells, proliferative cells of renewal tissues, some adult pluripotent stem cells, embryonic cells, but in most somatic cells is not detected. Re-expression or up-regulation of telomerase in tumours cells is considered as a critical step in cell tumorigenesis and telomerase is widely considered as a tumour marker and a target for anticancer drugs. Different approaches have been used in anticancer therapeutics targeting telomerase. Telomerase inhibitors can block directly Human TElomerase Reverse Transcriptase(h TERT) or Human TElomerase RNA telomerase subunits activity, or G-quadruplex and Sheltering com-plex components, shortening telomeres and inhibiting cell proliferation. Telomerase can become an immune target and GV1001, Vx-001, I540 are the most widespread vaccines used with encouraging results. Another method is to use h TERT promoter to drive suicide gene expression or to control a lytic virus replication. Recently telomerase activity was used to activate pro-drugs such as Acycloguanosyl 5'-thymidyltriphosphate, a synthetic ACV-derived molecule when it is activated by telomerase it does not require any virus or host active immune response to induce suicide gene therapy. Advantage of all these therapies is that target only neoplastic cells without any effects in normal cells, avoiding toxicity and adverse effects of the current chemotherapy. However, as not all the approaches are equally efficient, further studies will be necessary. | Lucia Picariello Cecilia Grappone Simone Polvani Andrea Galli | 2014 | World Journal of Pharmacology2014，3，4： | 3 |
| 6 | Peroxisome Proliferator-Activated Receptor and Retinoic X Receptor in Alcoholic Liver Disease显示文摘 | Tommaso Mello Simone Polvani Andrea Galli James P. Hardwick | 2009 | PPAR Research2009，，： | 2 |
| 7 | PPAR γ and Oxidative Stress: Con( β ) Catenating NRF2 and FOXO显示文摘 | Simone Polvani Mirko Tarocchi Andrea Galli Paul Drew | 2012 | PPAR Research2012，，： | 1 |
| 8 | Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus–transgenic mice by peroxisome proliferator‐activated receptor γ–independent regulation of nucleophosmin显示文摘 | Andrea Galli Elisabetta Ceni Tommaso Mello Simone Polvani Mirko Tarocchi Francesca Buccoliero Francesca Lisi Laura Cioni Barbara Ottanelli Valeria Foresta Guido Mastrobuoni Gloriano Moneti Giuseppe Pieraccini Calogero Surrenti Stefano Milani | 2010 | Hepatology2010，，2： | 1 |
| 9 | PPAR γ and Oxidative Stress: Con( β ) Catenating NRF2 and FOXO显示文摘 | Simone Polvani Mirko Tarocchi Andrea Galli Paul Drew | 2012 | PPAR Research2012，，： | 1 |
| 10 | COUP‐TFII in pancreatic adenocarcinoma: Clinical implication for patient survival and tumor progression显示文摘 | Simone Polvani Mirko Tarocchi Sara Tempesti Tommaso Mello Elisabetta Ceni Francesca Buccoliero Massimo D’Amico Vieri Boddi Marco Farsi Silvia Nesi Gabriella Nesi Stefano Milani Andrea Galli | 2014 | Int. J. Cancer2014，，7： | 1 |
| 11 | COUP‐TFII in pancreatic adenocarcinoma: Clinical implication for patient survival and tumor progression显示文摘 | Simone Polvani Mirko Tarocchi Sara Tempesti Tommaso Mello Elisabetta Ceni Francesca Buccoliero Massimo D’Amico Vieri Boddi Marco Farsi Silvia Nesi Gabriella Nesi Stefano Milani Andrea Galli | 2014 | Int J Cancer2014，，7： | 1 |
| 12 | Gastric and duodenal polyps in familial adenomatous polyposis patients: Conventional endoscopy vs virtual chromoendoscopy(fujinon intelligent color enhancement) in dysplasia evaluation显示文摘AIM To test the fujinon intelligent color enhancement(FICE) in identifying dysplastic or adenomatous polyps in familial adenomatous polyposis(FAP) patients.METHODS Seventy-six consecutive FAP patients, already treated by colectomy and members of sixty-five families, were enrolled. A FICE system for the upper gastro-intestinal tract with an electronic endoscope system and a standard duodenoscope(for side-viewing examination) were used by two expert examiners. Endoscopic resection was performed with diathermic loop for polyps ≥ 6 mm and with forceps for polyps < 6 mm. Formalin-fixed biopsy specimens were analyzed by two expert gastrointestinal pathologists blinded to size, location and number of FAPassociated fundic gland polyps.RESULTS Sixty-nine(90.8%) patients had gastric polyps(34 only in the corpus-fundus, 7 only in the antrum and 28 in the whole stomach) and 52(68.4%) in duodenum(7 in the bulb, 35 in second/third duodenal portion, 10 both in the bulb and the second portion of duodenum). In the stomach fundus after FICE evaluation, 10 more polyps were removed from 10 patients for suspicious features of dysplasia or adenomas, but they were classified as cystic fundic gland after histology. In the antrum FICE identified more polyps than traditional endoscopy, showing a better tendency to identify adenomas and displastic areas. In the duodenum FICE added a significant advantage in identifying adenomas in the bulb and identified more polyps in the Ⅱ/Ⅲ portion.CONCLUSION FICE significantly increases adenoma detection rate in FAP patients but does not change any Spigelman stage and thus does not modify patient's prognosis and treatment strategies. | Gabriele Lami Andrea Galli Giuseppe Macrì Emanuele Dabizzi Maria Rosa Biagini Mirko Tarocchi Luca Messerini Rosa Valanzano Stefano Milani Simone Polvani | 2017 | World Journal of Clinical Oncology2017，8，2： | 1 |
| 13 | Telomerase reactivation is associated with hepatobiliary and pancreatic cancers显示文摘Background:Human telomerase reverse transcriptase(hTERT)and its components play a significant role in cancer progression,but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases;increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic diseases.Data sources:We performed a PubMed search with the following keywords:telomerase,hepatocellular carcinoma,cholangiocarcinoma,pancreatic adenocarcinoma by December 2019.We reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic diseases.Results:Telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers,as a predictor for prognosis and a promising therapeutic target.Conclusions:Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases. | Vito Sansone Marco Le Grazie Jenny Roselli Simone Polvani Andrea Galli Francesco Tovoli Mirko Tarocchi | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，5： | 0 |
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