HEPATIC EXPRESSION OF CYCLOOXYGENASE-2 IN NON-ALCOHOLIC FATTY LIVER DISEASE

Cationic SLN for siRNA and DNA plasmid delivery in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths. For the treatment of HCC several drugs are under development, but the only one with proven survival benefit is sorafenib. This agent is a multikinase inhibitor that blocks Raf signaling and VEGF, PDGF and c-Kit. It has antiproliferative and antiangiogenic activity and delays tumor progression [1,2]. Moreover, systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutic strategies. At this purpose a large number of viral and non-viral vectors have been studied and applied as systems of stable transfec…

GRP78 POLYMORPHISM rs430397 IS ASSOCIATED WITH HEPATOCELLULAR CARCINOMA IN A SOUTHERN ITALIAN POPULATION

Ihnibitor of Apoptosis Proteins (IAPs) as a new possible therapeutic targets in hepatocellular cancer.

NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance

AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…

Development of nimesulide loaded solid lipid nanoparticles.

Yin Yang 1 and raf-1 Kinase Inhibitory Protein Status in Hepatocellular carcinoma: Future Perspectives

We focus on to the role of the transcription factors NF-κB and Yin Yang 1 (YY1) and of Raf-1 kinase inhibitory protein (RKIP) in hepatocellular carcinoma (HCC). YY1, whose expression is enhanced by NF-κB, favors tumorigenesis. RKIP inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist and there is separate evidence that relevant increases in YY1 and reductions in RKIP occur in HCC. In a recent study on clinical HCC, we found that, indeed, the ratio of YY1 to RKIP mRNA and protein expression is very frequently profoundly inverted in tumors compared with adjacent tissues. Hyperactivation of YY1 in tum…

Cationic solid lipid nanoparticles complexed with genetic material for liver tumor treatment

Concept Gene therapy is a growing field of medicine with great potential for the treatment of several diseases and it is based on the delivery of nucleic acids (DNA, RNA, etc.,) to specific cells. To achieve their therapeutic effects, the nucleic acids need to cross several biological barriers and be protected from the degradation by nucleases, present in biological fluids and intracellular compartments, to successfully gain access to their intracellular targets. To overcome these hurdles, it is necessary to deliver the genetic material with biocompatible carriers able to facilitate its translocation across the cell membranes and protect it from being degraded while circulating in the blood…

Antitumor effects of curcumin and of its combination with cisplatin or doxorubicin on human hepatic cancer cells: possible relationship to NF-kB activation and IAP gene expression.

DNA PLASMID DELIVERY INTO HEPATOCELLULAR CARCINOMA CELLS BY COMPLEXATION WITH SOLID LIPID NANOPARTICLES

Delivery of shNupr1 plasmid by solid lipid nanoparticles reduces the expression of Nupr1 gene in hepatocellular carcinoma cells

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 …

Targeting NUPR1 with the Small Compound ZZW-115 Is an Efficient Strategy to Treat Hepatocellular Carcinoma

International audience; HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor …

Delivery of shRNA plasmid DNA by cationic solid lipid nanoparticles for gene silencing in human hepatocarcinoma cells

Expression of HIP/PAP mRNA in Human Hepatoma Cell Lines

The present study attempts to shed more light on the role of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) in hepatoma cells. We initially examined, by reverse transcription-polymerase chain reaction (RT-PCR), the HIP/PAP transcripts present in human hepatoma cell lines of different origins and with different grades of differentiation and genetic profiles. We also used DNA sequencing analysis to investigate the structure of the HIP/PAP gene. Further investigation is necessary to define the role of HIP/PAP during the development of human hepatocellular carcinoma and to ascertain whether the use of different transcripts is helpful in regulating HIP/PAP expression …

Preparation, characterization and biological evaluation of Nanostructured Lipid Carriers (NLCs) conteining sorafenib

Inhibitor of apoptosis proteins (IAPs) as new possible therapeutic targets in hepatocellular cancer

Cationic Solid Lipid Nanoparticles (SLN) for shNupr1 plasmid delivery in the treatment of hepatocellular carcinoma (HCC)

Response to the Letter to the editor regarding “Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carcinoma” by Jiong Lin

Antitumor activity of the novel small molecule Akt inhibitor SC66 in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide characterized by poor and often limited or no response to current drug therapies. The PI3K/Akt/mTOR pathway is a key regulator of cell proliferation and survival. Alterations in this pathway have been reported in many types of human cancer, including HCC. It has become evident that Akt inhibitors have great potential in cancer treatment. SC66 is a new allosteric Akt inhibitor that facilitates ubiquitination of Akt, favoring its degradation via the proteasome, thus inhibiting Akt signaling. In the present study, we investigated the anticancer activity of SC66 in HCC cell lines (HepG2, Huh7, Hep3B, PLC/PRF/5 and HA22T/VG…

Antitumor effects of curcumin and of its combinations with cisplatin or doxorubicin on human hepatic cancer cells: Possible relationship to NF-kB activation and IAP gene expression

ENTRAPMENT OF TYRPHOSTIN AG 14-78 INTO LIPID NANOPARTICLES IMPROVES ITS ANTITUMOR ACTIVITY AGAINST HUMAN HEPATOCARCINOMA CELLS

Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma

Interleukin-6 plays a central role in regulating the immune system, hematopoiesis, and acute phase reaction. It interacts with a receptor complex consisting of a specific ligand-binding protein (IL-6R, gp80) and a signal transduction protein (gp130). In this report, serum levels of IL-6 and a soluble form of the interleukin-6 receptor (sIL-6R) were evaluated in patients with hepatocellular carcinoma. The correlation between IL-6 and sIL-6R values, the stage of hepatocellular carcinoma, and main liver function tests was also studied.

NANOSTRUCTURED LIPID CARRIERS (NLC) AS DRUG DELIVERY SYSTEMS FOR SORAFENIB

The selective COX-1 inhibitor SC-560 inhibits cell growth and induces apoptosis in human hepatocellular carcinoma cells

Detection of vitellogenin in a subpopulation of sea urchin coelomocytes.

Sea urchin vitellogenin is a high molecular weight glycoprotein, which is the precursor of the major yolk protein present in the unfertilized egg. Vitellogenin processing into the major yolk protein and its further enzymatic cleavage during sea urchin embryonic development, has been extensively described, and the adhesive properties of the processed molecule have been studied. The function of vitellogenin in the adult, where it has been found in the coelomic fluid of both male and female individuals, is still unknown, although its role on promoting the adhesion of embryonic cells has been shown. In this report we describe the detection of vitellogenin in lysates of whole circulating coelomo…

Encapsulation of sorafenib into lipid nanoparticles improves its antitumor activity.

Effects of kind and amount of surfactants on physical-chemical properties of cationic solid lipid nanoparticles (SLN) for the treatment of hepatocellular carcinoma.

Lipid nanocarrier for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Unlike most solid tumors the incidence and mortality of HCC have increased in the United States and Europe in the past decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies [1,2]. To improve the delivery of therapeutic agents to tumor cells in vivo it’s necessary to overcome several problems, such as drug resistance at the tumor level due to physiological barriers (non cellular based mechanism), drug resistance at the cellular level (cellular mechanism), drug distribution, biotransformation and clearance of antic…

Antitumor effects of curcumin in human hepatic cancer cells: Analysis of their relationship to inhibition of NF-kB and pro-survival gene expression.