References of "Princen, Frederic"
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See detailRat Gap Junction Connexin-30 Inhibits Proliferation of Glioma Cell Lines
Princen, Frederic; Robe, Pierre ULg; Gros, D. et al

in Carcinogenesis (2001), 22(3), 507-13

Connexins, the structural components of gap junctions, control cell growth and differentiation and are believed to belong to a family of tumour suppressor genes. Studies on connexin localization in brain ... [more ▼]

Connexins, the structural components of gap junctions, control cell growth and differentiation and are believed to belong to a family of tumour suppressor genes. Studies on connexin localization in brain showed that several of these proteins were expressed in distinct compartments of the brain in a cell-type specific manner, indicating that different gap junctions play specific roles in the physiology of the mammalian brain. In this report, we first cloned rat connexin-30 cDNA from brain and showed that it was expressed in long-term primary culture of rat astrocytes. In order to examine the potential role of connexin-30 in tumour cell proliferation, we transfected the connexin-30 cDNA into two rat glioma cell lines (9L and C6) which have lost its expression. Transfected clones adequately expressed membrane-bound connexin-30 protein. Connexin-30-expressing clones showed slower growth, lower DNA synthesis and reduced proliferation in soft agar as compared with the parental and control cells. We concluded that connexin-30 may also probably be considered as a tumour suppressor in rat gliomas. [less ▲]

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See detailCombined Suicide and Cytokine Gene Therapy for Peritoneal Carcinomatosis
Lechanteur, Chantal ULg; Delvenne, Philippe ULg; Princen, Frédéric et al

in Gut (2000), 47(3), 343-8

BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene. AIMS: The efficacy of ... [more ▼]

BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene. AIMS: The efficacy of a therapy combining a suicide gene (herpes simplex virus type I thymidine kinase (HSV-TK)) and cytokine genes was investigated in a model of peritoneal carcinomatosis induced by colon carcinoma cells in syngeneic rats. MATERIAL AND METHODS: Pre-established macroscopic tumours in BDIX rats were treated by intraperitoneal injections of retrovirus producing cells (FLYA13 TK, FLYA13 granulocyte macrophage-colony stimulating factor (GM-CSF), FLYA13 interleukin 12 (IL-12)) and ganciclovir (GCV). RESULTS: TK/GCV treated animals showed a slight increase in survival time (72 days) compared with the control group (63 days) while the association of cytokine and TK/GCV gene therapy resulted in significantly improved survival, with a large proportion of animals remaining tumour free on day 480 (60% and 40% for TK/GCV/GM-CSF and TK/GCV/IL-12 treated animals, respectively). Histological analysis of treated animals showed that the remaining tumour nodes were infiltrated by mononuclear cells but no major differences were observed between the various treatments. Immunohistochemical analysis revealed that lymphoid CD4(+) and CD8(+) T cells as well as macrophages accumulated outside untreated tumour nodes while CD8(+) and CD25(+) activated T cells and macrophages heavily infiltrated the tumours after the different treatments. CONCLUSIONS: Our data indicate that combined suicide and cytokine gene therapy is a powerful approach for the treatment of macroscopic peritoneal carcinomatosis. [less ▲]

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See detailPharmacological Modulation of the Bystander Effect in the Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy System: Effects of Dibutyryl Adenosine 3',5'-Cyclic Monophosphate, Alpha-Glycyrrhetinic Acid, and Cytosine Arabinoside
Robe, Pierre ULg; Princen, Frédéric; Martin, Didier ULg et al

in Biochemical Pharmacology (2000), 60(2), 241-9

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield ... [more ▼]

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield. Fortunately, the gap junction-dependent diffusion of phosphorylated ganciclovir metabolites from transfected cells to their neighbors proved to enhance the overall benefit of this strategy. However, as tumor cells are often gap junction-deficient, we sought to restore this property pharmacologically and hence to improve the efficacy of the treatment. We demonstrated that this approach was feasible in glioblastoma cells using dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (100 microM) as a pharmacological inducer of gap junctions. alpha-Glycyrrhetinic acid (25 microM), on the other hand, strongly inhibited both gap junction-mediated intercellular communication and the bystander effect, thus confirming the role of gap junctions in HSV-tk-mediated bystander killing. Using cytosine arabinoside as a growth inhibitor, we underlined the role of tumor cell proliferation in the sensitivity of HSV-tk-transfected cells to ganciclovir and demonstrated its correlation with the importance of the bystander effect. [less ▲]

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See detailAntitumoral Vaccination with Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-12-Expressing Dhd/K12 Colon Adenocarcinoma Cells
Lechanteur, Chantal ULg; Moutschen, Michel ULg; Princen, Frederic et al

in Cancer Gene Therapy (2000), 7(5), 676-82

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and ... [more ▼]

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model of peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral cells engineered to produce IL-12 or GM-CSF did not generate any tumors, whereas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL-12-expressing DHD/K12 cells also protected against tumors derived from coinjected parental cells. To test whether cytokine-producing cells could elicit a memory antitumoral immune response, animals received a challenge with parental DHD/K12 cells 35 days after the injection of proliferating or irradiated DHD/K12 engineered cells. Under our experimental conditions, irradiated tumor cells did not generate any antitumoral immunity. In contrast, tumor development was delayed and survival increased in the animals vaccinated with cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocyte response against DHD/K12 parental cells was observed after vaccination with GM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or GM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection of colorectal cancer. [less ▲]

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See detailCytosine Deaminase Suicide Gene Therapy for Peritoneal Carcinomatosis
Bentires-Alj, M.; Hellin, A. C.; Lechanteur, Chantal ULg et al

in Cancer Gene Therapy (2000), 7(1), 20-6

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal ... [more ▼]

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis. [less ▲]

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See detailSimilar Efficiency of DNA-Liposome Complexes and Retrovirus-Producing Cells for Hsv-Tk Suicide Gene Therapy of Peritoneal Carcinomatosis
Princen, Frederic; Lechanteur, Chantal ULg; Lopez, Marie-Josée ULg et al

in Journal of Drug Targeting (2000), 8(2), 79-89

Several experimental approaches have been tested for suicide gene delivery into tumor cells, including viral and non-viral vectors. In this study, we compared the efficiency of Herpes Simplex Virus type 1 ... [more ▼]

Several experimental approaches have been tested for suicide gene delivery into tumor cells, including viral and non-viral vectors. In this study, we compared the efficiency of Herpes Simplex Virus type 1 thymidine kinase gene (HSV-tk) delivery by retrovirus-producing cells and DNA/liposome complexes for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colorectal adenocarcinoma cells. After in vitro determination of the best transduction conditions, rats were treated with multiple intraperitoneal injections of plasmid DNA containing one or two copies of CMV-driven HSV-tk gene (pCMV-TK and p(CMV-TK)2, respectively) associated with LipofectAMINE, each injection being followed by a Ganciclovir (GCV) course. Animals treated by DNA/liposome complexes and GCV or with retrovirus-producing cells and GCV showed a similar increase of survival as compared to the control group. After DNA/ liposome injections, expression of the tk transgene was detected in tumor nodes (epiploon) and also in liver, lung, spleen, bowels and brain. The expression was not homogeneous throughout the different organs and most likely reflected the transfection of only a limited number of cells. [less ▲]

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See detailA Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect
Princen, Frederic; Robe, Pierre ULg; Lechanteur, Chantal ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (1999), 5(11), 3639-44

Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but ... [more ▼]

Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described. In this study, we analyzed the mechanisms of the bystander effect in two cell lines exhibiting different capacities of communication (DHD/K12 and 9L). The 9L cells exhibited a very good bystander effect, which was completely blocked by a long-term inhibitor of GJIC, 18 alpha-glycyrrhetinic acid. DHD/K12 cells exhibited a moderate bystander effect that was not abolished by 18 alpha-glycyrrhetinic acid or 1-octanol, another strong inhibitor of GJIC. Interestingly, we also observed a bystander effect in cultures where HSV-tk-expressing DHD/K12 cells were physically separated from their untransfected counterparts but grown in the same medium. Moreover, the transfer of filtered conditioned medium from GCV-treated HSV-tk-expressing DHD/K12 cells to DHD/K12 parental cells induced a decrease of survival in a concentration-dependent manner, suggesting that the bystander effect in this cell line was mediated by a soluble factor. [less ▲]

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See detailIkappab-Alpha Enhances Transactivation by the Hoxb7 Homeodomain-Containing Protein
Chariot, Alain ULg; Princen, Frédéric; Gielen, Jacques et al

in Journal of Biological Chemistry (1999), 274(9), 5318-25

Combinatorial interactions between distinct transcription factors generate specificity in the controlled expression of target genes. In this report, we demonstrated that the HOXB7 homeodomain-containing ... [more ▼]

Combinatorial interactions between distinct transcription factors generate specificity in the controlled expression of target genes. In this report, we demonstrated that the HOXB7 homeodomain-containing protein, which plays a key role in development and differentiation, physically interacted in vitro with IkappaB-alpha, an inhibitor of NF-kappaB activity. This interaction was mediated by the IkappaB-alpha ankyrin repeats and C-terminal domain as well as by the HOXB7 N-terminal domain. In transient transfection experiments, IkappaB-alpha markedly increased HOXB7-dependent transcription from a reporter plasmid containing a homeodomain consensus-binding sequence. This report therefore showed a novel function for IkappaB-alpha, namely a positive regulation of transcriptional activation by homeodomain-containing proteins. [less ▲]

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See detailRepeated Cycles of Retrovirus-Mediated Hsvtk Gene Transfer Plus Ganciclovir Increase Survival of Rats with Peritoneal Carcinomatosis
Princen, Frédéric; Lechanteur, Chantal ULg; Lopez Y Cadenas, Miguel ULg et al

in Gene Therapy (1998), 5(8), 1054-60

Peritoneal carcinomatosis is a common clinical situation that requires novel therapeutic approaches. We investigated the efficiency of an HSVtk gene therapy for the treatment of peritoneal carcinomatosis ... [more ▼]

Peritoneal carcinomatosis is a common clinical situation that requires novel therapeutic approaches. We investigated the efficiency of an HSVtk gene therapy for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colon carcinoma cells. In this setting, the efficiency of two different retrovirus producing cell lines (GP+AmEnv12 and FLYA13) was compared. Rats treated with a single injection of retrovirus producing cells followed by a 5-day course of ganciclovir treatment showed an increased survival as compared with control animals. Animals treated with three injections of producing cells, each followed by a 4-5-day course of ganciclovir treatment, showed an increased survival as compared with control rats and with those treated with a single cycle of retrovirus producing cells plus ganciclovir. However, only a few animals remained tumor-free after day 180. There was no difference between the two producing cell lines in any of the experiments. RT-PCR demonstrated a faint expression of the tk transgene in the liver, spleen, epiploon, bowels and the lung of the animals injected with the HSVtk producing cells, reflecting most likely the transduction of only a limited number of cells. [less ▲]

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See detailHsv-1 Thymidine Kinase Gene Therapy for Peritoneal Carcinomatosis
Lechanteur, Chantal ULg; Princen, Frédéric; Lo Bue, S. et al

in Advances in Experimental Medicine and Biology (1998), 451

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See detailHsv-1 Thymidine Kinase Gene Therapy for Colorectal Adenocarcinoma-Derived Peritoneal Carcinomatosis
Lechanteur, Chantal ULg; Princen, Frédéric; Lo Bue, S. et al

in Gene Therapy (1997), 4(11), 1189-94

Peritoneal carcinomatosis is a common clinical situation which, in most cases, cannot be eradicated by surgery or chemotherapy. The feasibility of an HSV-TK-based suicide gene therapy for peritoneal ... [more ▼]

Peritoneal carcinomatosis is a common clinical situation which, in most cases, cannot be eradicated by surgery or chemotherapy. The feasibility of an HSV-TK-based suicide gene therapy for peritoneal carcinomatosis induced by DHD/K12 colon carcinoma cells was investigated. DHD/K12 cells stably expressing the tk gene were killed in vitro in the presence of low concentrations of ganciclovir, they exhibited a 'bystander effect' when mixed with TK-negative cells. BD-IX rats injected intraperitoneally, either directly or after surgical peritoneal irritations, with DHD/K12 cells developed peritoneal carcinomatosis within 2 weeks. Ganciclovir treatment of animals injected with DHD/K12-TK cells allowed a significant reduction of the tumor volume as well as a prolonged survival. Of these animals 35-40% showed a long-term disease-free survival after ganciclovir therapy. Residual or relapsing tumors could be explained by a low expression of the transgene as demonstrated by RT-PCR. [less ▲]

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See detailSeventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events
Jackers, Pascale ULg; Clausse, Nathalie; Fernandez, Maria-Teresa et al

in Biochimica et Biophysica Acta (1996), 1305(1-2), 98-104

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40 ... [more ▼]

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed in invasive and metastatic cancer cells and is associated with poor prognosis. Southern-blot analysis of human genomic DNA predicted multiple copies of the 37LRP/p40 gene. In this study, we report that the number of copies of this sequence in the human genome is 26 +/- 2. We have sequenced and analyzed 19 genomic clones corresponding to the 37LRP/p40 gene and found that they were all processed pseudogenes. They all lack intronic sequences and show multiple genetic alterations leading in some cases to the appearance of stop codons. Moreover, they all bear characteristic features of retroposons as the presence of a poly(A)-tail at their 3' end and short direct repeated flanking DNA sequences. None of the pseudogenes analyzed present cis-elements in their 5' flanking region such as TATA or GC boxes. Our date reveal that over 50% of the 37LRP/p40 gene copies are pseudogenes most probably generated by retropositional events. The finding of multiple pseudogenes for the 37LRP/p40 suggests that the accumulation of several copies of this gene might have given a survival advantage to the cell in the course of evolution. [less ▲]

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