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Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions

World Journal of Gastroenterology 2017年第32期23卷 5875-5886页

作者： Guido Giordano massimo pancione Nunzio Olivieri Pietro Parcesepe Marianna Velocci Tania Di Raimo Luigi Coppola Giuseppe Toffoli Mario Rosario D’Andrea Medical Oncology Unit San Filippo Neri Hospital CRO Aviano National Cancer Institute Department of Sciences and Technologies University of Sannio Department of Biochemistry and Molecular Biology II Faculty of PharmacyComplutense University Department of Biology University of Naples Department of Pathology and Diagnostics University of Verona Strada Anatomic Pathology Unit San Filippo Neri00135 RomaItaly Experimental and Clinical Pharmacology Unit CRO-National Cancer Institute Via F

Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.

关键词： Nano 白朊 bound-paclitaxel 胰腺的癌症变形疾病 Gemcitabine Folfirinox

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emerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer

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World Journal of Gastroenterology 2014年第23期20卷 7137-7151页

作者： Lina Sabatino massimo pancione Carolina Votino Tommaso Colangelo Angelo Lupo Ettore Novellino Antonio Lavecchia Vittorio Colantuoni Department of Sciences and Technologies University of Sannio Department of Pharmacy "Drug Discovery" LaboratoryUniversity of Naples "Federico Ⅱ"80131 NaplesItaly

Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer(CRC)initiation and *** genome-wide data have confirmed that in CRC this pathway is one of the most frequently modified by genetic or epigenetic alterations affecting almost 90%of Wnt/β-catenin gene members.A major challenge is thus learning how the corrupted coordination of this pathway is tied to other signalings to enhance cell *** proliferator activated receptorγ(PPARγ)is emerging as a growth-limiting and differentiation-promoting *** tumorigenesis it exerts a tumor suppressor role and is potentially linked with the Wnt/β-catenin *** on these results,the identification of new selective PPARγmodulators with inhibitory effects on the Wnt/β-catenin pathway is becoming an interesting ***,in fact,these molecules display such properties,new research avenues would be opened aimed at developing new molecular targeted ***,we review the basic principles and present new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ***,we discuss the advances in our understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PPARγagonists endowed with Wnt/β-catenin inhibitory effects to be used as therapeutic and/or preventive agents.

关键词： Colorectal cancer Wnt/β-catenin pathway Peroxisome

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