Characterization of effector components from the humoral and cellular immune response stimulated by melanoma cells exhibiting modified IGF-1 expression.

Modified melanoma B16 cells inhibited in their IGF-1 expression (B16MOD), on the contrary to the IGF-1 fully expressed parental wild-type (B16WT) counterpart, were shown to stimulate humoral as well as cellular immune responses. Among humoral components, the neutralizing and complement-fixing antibodies of IgM and essentially IgG2 (a+b) isotypes exhibited in vitro and in vivo effects upon tumour growth, while the IgG1 antibody isotype promoted enhanced tumour proliferation. As for the cellular immunity, it was found that the T CD8(+) lymphocyte subpopulation remained the main potent and long lasting immune active effector regulating tumour growth.

Quinone-based polymers for label-free and reagentless electrochemical immunosensors: application to proteins, antibodies and pesticides detection.

Polyquinone derivatives are widely recognized in the literature for their remarkable properties, their biocompatibility, simple synthesis, and easy bio-functionalization. We have shown that polyquinones present very stable electroactivity in neutral aqueous medium within the cathodic potential domain avoiding side oxidation of interfering species. Besides, they can act as immobilized redox transducers for probing biomolecular interactions in sensors. Our group has been working on devices based on such modified electrodes with a view to applications for proteins, antibodies and organic pollutants using a reagentless label-free electrochemical immunosensor format. Herein, these developments are briefly reviewed and put into perspective.

Complex interplays in immune T-cell differentiation and developmental fate determination.

Aspects relevant to immune T-cell differentiation and fate determination have been examined and discussed in the context of transcription factors, initiating cytokines in association with cognate antigen activation. It appears that the differentiation optional program, in light of recent results related to genetic as well as epigenetic mechanisms, is not predetermined and irreversibly fixed; rather, there is some degree of flexibility allowing the manipulation of remodeling the already differentiated effector cell subsets/lineages. From the progress obtained it will be possible, in the near future, to tailor and obtain various well-defined and efficient immune effector cell subsets/cell lineages for translational applications in autoimmunity, infectious diseases, graft rejection as well as cancer in safe conditions.

Stimulation of anti-melanoma immune effectors via modified tumour cells exhibiting inhibited IGF-I and low CD9.

Modified melanoma cells (B16-F0.MOD) characterized by inhibited IGF-I, CD9 low but not their wild-type counterparts (B16-F0.WT), IGF-I positive, CD9 high, were shown to be immunogenic for syngeneic hosts. C57BL/6 syngeneic recipients vaccinated with B16-F0.MOD cells developed immune effectors that were observed at the humoral as well as cellular levels. These immune effectors were shown to be capable of controlling in vitro tumour growth and in vivo tumour progression.

A new putative target for antisense gene therapy of glioma: glycogen synthase.

The treatment of malignant brain gliomas remains a challenge, despite the availability of the classical triad of surgery, radiotherapy, and chemotherapy. There is thus the need for investigations into other forms of treatment strategies, such as gene therapy. Using antisense technology we have targeted glycogen metabolism, since malignant astrocytes present a high content of glycogen. In vitro rat C6­glioma cells, transfected with antisense glycogen synthase (C6­AS cells) exhibited a decreased expression of glycogen synthase and reduced activity of glycogen synthesis, along with attenuated invasiveness. In vivo tumors induced by C6­AS cells in nude mice exhibited a significant reduction in tumor growth compared with controls. This reduction could be mediated by the induction of MCH­I expression. The inhibition of glycogen synthesis by antisense glycogen synthase validates a putative target and a new approach for further study to advance the much­needed efficacy of intervention strategies for malignant gliomas.

In vitro assessment of renal toxicity and inflammatory events of two protein phosphatase inhibitors cantharidin and nor-cantharidin.

In China, cantharidin has been reported to be active against various human cancers, but with severe side effects such as nephrotoxicity. In order to reduce this toxicity, its demethylated analogue nor-cantharidin has been synthesized and used in cancer therapy, but with only few data regarding safety assessment. The aim of this study was to compare the in vitro effects of cantharidin and nor-cantharidin on renal toxicity and on inflammatory events associated with tumoural process where protein phosphatases could be involved (energy status, prostanoid production, glutathione and nitrite contents) on RAW 264.7 and LLC-PK1 cells. In macrophages, both cantharidin and nor-cantharidin decreased cell viability, in a concentration- and time-dependent manner. However, IC50 was lower with cantharidin than with nor-cantharidin. These two drugs significantly decreased the ATP level after 24 hr incubation. However, ATP decreased much more with cantharidin (up to 4 times) than with nor-cantharidin. When control macrophages were activated with lipopolysaccharide+interferon-gamma for 24 hr a significant increase in nitrite content and in prostanoids were observed. Addition of either drug decreased nitrite generation and prostanoids, however these decreases were greater with cantharidin than with nor-cantharidin. In LLC-PK1 cells, incubated with either cantharidin or nor-cantharidin, our results show significant differences between the two drugs, similar to those observed in peritoneal macrophages, except for GSH content with opposite variations in both cells. We provide a better understanding of the various mechanisms of cantharidin side effects, allowing an easier comparison with nor-cantharidin which could be an attractive therapeutic potential in cancer chemotherapy in western countries.

In vitro and in vivo immunotoxic and immunomodulatory effects of nonsupplemented and selenium-supplemented cigarette smoke condensate.

Cigarette smoke condensate has been evaluated for its in vitro and in vivo immunotoxic and immunomodulatory properties. It was found that cigarette smoke condensate used in vitro at concentration from 6.6 to 20 microg/ml exerted pronounced inhibitory effects upon cell surface antigen-presenting major histocompatibility complex class I (MHC-I) expression and immunoglobulin (Ig) synthesis. In vivo, i.p. administration of cigarette smoke condensate to C57BL/6 mice before challenging with ovalbumin (OVA) antigen, has led to a decrease of anti-OVA specific antibody response. This inhibition affected more Ig protein synthesis than membrane bound MHC-I expression. Supplementation with selenium (Se) significantly reduced the inhibitory effects both in vitro and in vivo.