Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL)

Fas ligand is a type II transmembrane protein which can induce apoptosis in Fas-expressing cells. Recent reports indicate that expression of FasL in transplanted cells may cause graft rejection and, on the other hand, tumor cells may lose their tumorigenicity when they are engineered to express FasL. These effects could be related to recruitment of neutrophils by FasL with activation of their cytotoxic machinery. In this study we investigated the antitumor effect of allogenic fibroblasts engineered to express FasL. Fibroblasts engineered to express FasL (PA317/FasL) did not exert toxic effects on transformed liver cell line (BNL) or colon cancer cell line (CT26) in vitro, but they could abrogate their tumorigenicity in vivo. Histological examination of the site of implantation of BNL cells mixed with PA317/FasL revealed massive infiltration of polymorphonuclear neutrophils and mononuclear cells. A specific immune protective effect was observed in animals primed with a mixture of BNL or CT26 and PA317/FasL cells. Rechallenge with tumor cells 14 or 100 days after priming resulted in protection of 100 or 50% of animals, respectively. This protective effect was due to CD8+ cells since depletion of CD8+ led to tumor formation. In addition, treatment of pre-established BNL tumors with a subcutaneous injection of BNL and PA317/FasL cell mixture at a distant site caused significant inhibition of tumor growth. These data demonstrate that allogenic cells engineered with FasL are able to abolish tumor growth and induce specific protective immunity when they are mixed with neoplastic cells

Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12

Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans

Multilocus ISSR Markers Reveal Two Major Genetic Groups in Spanish and South African Populations of the Grapevine Fungal Pathogen Cadophora luteo-olivacea

Cadophora luteo-olivacea is a lesser-known fungal trunk pathogen of grapevine which has been recently isolated from vines showing decline symptoms in grape growing regions worldwide. In this study, 80 C. luteo-olivacea isolates (65 from Spain and 15 from South Africa) were studied. Inter-simple-sequence repeat-polymerase chain reaction (ISSR-PCR) generated 55 polymorphic loci from four ISSR primers selected from an initial screen of 13 ISSR primers. The ISSR markers revealed 40 multilocus genotypes (MLGs) in the global population. Minimum spanning network analysis showed that the MLGs from South Africa clustered around the most frequent genotype, while the genotypes from Spain were distributed all across the network. Principal component analysis and dendrograms based on genetic distance and bootstrapping identified two highly differentiated genetic clusters in the Spanish and South African C. luteo-olivacea populations, with no intermediate genotypes between these clusters. Movement within the Spanish provinces may have occurred repeatedly given the frequent retrieval of the same genotype in distant locations. The results obtained in this study provide new insights into the population genetic structure of C. luteo-olivacea in Spain and highlights the need to produce healthy and quality planting material in grapevine nurseries to avoid the spread of this fungus throughout different grape growing regions

Analysis of LINGO1 (rs9652490) polymorphism in sporadic Parkinson's disease in a Polish population, and a meta-analysis

10.1016/j.neulet.2010.01.055Neuroscience Letters472153-55NELE

Essential phospholipids in fatty liver: a scientific update

Karl-Josef Gundermann,1 Simon Gundermann,2 Marek Drozdzik,1 VG Mohan Prasad3 1Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland; 2Department of Radiology, Hospital Hohenlind, Cologne, Germany; 3VGM Hospital Institute of Gastroenterology, Coimbatore, India Aim: Although essential phospholipids (EPL) from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases (FLDs) of different origin, are still widely unknown and a matter of continuous active research. The aim of this article is to review, discuss, and summarize the available results of EPL in the treatment of FLD. Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations for relevant hepatogastroenterological articles published between 1988 and 2014. We searched for and reviewed only those papers that indicated minimum extraction amount of 72% (3-sn-phosphatidyl)choline from soybean as being necessary to treat patients with a considerable amount of 1,2-dilinoleoylphosphatidylcholine as a key component in EPL. Results: EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane-dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, antiapoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver. Conclusion: Pharmacological and clinical results confirm the efficacy of EPL in the treatment of FLD. Keywords: fatty liver disease, essential phospholipids, dilinoleoylphosphatidylcholine, membran