References of "DELVENNE, Philippe"
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See detailINFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Poster (2013, May 30)

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion
Renoux, Virginie; Bisig, Bettina; Langers, Inge ULg et al

Poster (2013, May)

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK-cell infiltration in HPV- associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK-cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-a and IFN-g) in the presence of HPV-VLPs. Using flow cytometry and microscopy, we observed that NK-cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16- NK-cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV–VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailHERPES SIMPLEX VIRUS REACTIVATION AND DENTAL PROCEDURES
EL HAYDERI, Lara ULg; DELVENNE, Philippe ULg; ROMPEN, Eric ULg et al

in Clinical Oral Investigations (2013)

Objectives : Dental extraction is reportes to trigger recurrent herpes labialis (RHL). Aim : This aims to prospectively study the clinical occurrence of RHL and the oral herpes simplex virus type 1 (HSV-1 ... [more ▼]

Objectives : Dental extraction is reportes to trigger recurrent herpes labialis (RHL). Aim : This aims to prospectively study the clinical occurrence of RHL and the oral herpes simplex virus type 1 (HSV-1) viral shedding before and 3 days after different dental procedures. Materials and methods : Oral HSV-1 DNA was measured by real-time PCR before and 3 days after dental procedures of the inferior dentition in 57 immunocometent patients (mean age 32.4 years) who were selected and divided into four distinct subgroups (dental inspection without anesthesia, n=14; molar extraction under local anesthesia, n=15; and molar extraction under general anesthesia, n=9) and compared to 32 healthy controls (mean age 33 years). Results : None of the patients suffered from RHL at day 3. Oral HSV-1 DNA was detected before and after procedure in 1.7 % (1/57) and 5.3 % (3/57), respectively [dental inspection without anesthesia, 5.3 % (1/19); molar extraction under local anesthesia, 6.7 % (1/15); and molar extraction under general anesthesia, 11 % (1/9)]. None of the controls presented RHL or detectable oral HSV-1 DNA. There was no statistically significant difference between the study groups and controls. [less ▲]

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See detailClinical Utility of an Epigenetic Assay to Detect Occult Prostate Cancer in Histopathologically Negative Biopsies: Results of the MATLOC Study.
Stewart, Grant D.; Van Neste, Leander; DELVENNE, Philippe ULg et al

in Journal of Urology (The) (2013), 189(3), 1110-1116

PURPOSE: Concern over possible false negative histopathology of prostate biopsies often leads to re-biopsy. A quantitative methylation-specific PCR (QMSP) assay panel, including GSTP1,APC and RASSF1 ... [more ▼]

PURPOSE: Concern over possible false negative histopathology of prostate biopsies often leads to re-biopsy. A quantitative methylation-specific PCR (QMSP) assay panel, including GSTP1,APC and RASSF1, could serve to increase the sensitivity to detect cancer over pathologic review alone, leading towards a high negative predictive value (NPV) and a decrease of unnecessary repeat biopsies. MATERIALS AND METHODS: The MATLOC (Methylation Analysis To Locate Occult Cancer) study blindly tested archived prostate biopsy needle core tissue samples of 498 subjects from the UK and Belgium with histopathologically negative prostate biopsies followed by either a positive (cases) or negative (controls) repeat biopsy within 30 months. The clinical performance of the epigenetic marker panel, emphasizing NPV, was assessed and cross-validated. Multivariate logistic regression was used to evaluate all risk factors. RESULTS: The epigenetic assay performed on the first, negative biopsies from this retrospective review cohort resulted in an NPV of 90% (95% CI, 87-93%). In a multivariate model, correcting for age, PSA, DRE and histopathological characteristics of the first biopsy, the epigenetic assay proved to be a significant, independent predictor of patient outcome with an odds ratio of 3.17 (95% CI, 1.81-5.53). CONCLUSIONS: A multiplex QMSP assay determining the methylation status of GSTP1,APC and RASSF1is strongly associated with the outcome of a repeat biopsy up to 30 months after an initial negative biopsy in men with suspicion of prostate cancer. The addition of this epigenetic assay could improve the prostate cancer diagnostic process and reduce unnecessary repeat biopsies. [less ▲]

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See detailTumor microenvironment converts plasmacytoid dendritic cells into immunosuppressive/tolerogenic cells: insight into the molecular mechanisms
Demoulin, Stéphanie ULg; Herfs, Michael ULg; Delvenne, Philippe ULg et al

in Journal of Leukocyte Biology (2013), 93(3), 343-352

Human pDCs represent a rare population of circulating cells characterized by a rapid and massive TLR-dependent secretion of type I IFN in response to pathogenic agents or danger signals. Through their ... [more ▼]

Human pDCs represent a rare population of circulating cells characterized by a rapid and massive TLR-dependent secretion of type I IFN in response to pathogenic agents or danger signals. Through their capacity to bring together innate and adaptive immunity and to secrete soluble factors controlling cancer development, these cells could represent important actors in antitumor immunity. However, accumulating evidence suggests that pDCs recruited to the tumor microenvironment often display a nonactivated state and are associated with the development and maintenance of immunosuppression. Here, we present an overview of neoplastic lesions associated with an infiltration of immunosuppressive/ tolerogenic pDC. Moreover, as the proper response of pDC against cancer depends on a critical balance between immune-activating and immune-suppressing mechanisms, we summarize current knowledge about the molecular pathways developed by tumors to prevent antitumoral pDC immune responses. A better understanding of the mechanisms regulating pDC function in tumors could aid in the development of new therapies. Indeed, effective cancer vaccines or therapies could combine immunoactivating strategies (i.e., TLR agonists) with elimination of immune-suppressing mechanisms, leading to pDC reprogramming and thus, allowing tumor rejection in a clinical setting. [less ▲]

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See detailRole of Gamma Delta T cells in HPV-induced Cancer Progression
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Poster (2013, January 28)

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See detailInterleukin-32 expression is associated with a poorer prognosis in head and neck squamous cell carcinoma.
Guenin, Samuel; Mouallif, Mustapha ULg; Hubert, Pascale ULg et al

in Molecular Carcinogenesis (2013), 53(8), 667-673

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes ... [more ▼]

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes carcinogenesis as well as the formation of metastasis. Indeed, proinflammatory mediators are known to stimulate the expression of specific transcription factors such as Snai1 and to increase the ability of tumor cells to migrate into distant organs. The atypical interleukin-32 (IL32) was mainly described to exacerbate inflammatory responses in rheumatoid arthritis and inflammatory bowel diseases. IL32 is expressed in various cancers but its role in HNSCC physiology is still unexplored. Here, we analyzed the expression of IL32 and its implication on HNSCC aggressiveness. We showed that patients with tumor expressing high amounts of IL32 exhibit decreased disease-free periods (20.5 mo vs. 41 mo, P = 0.0041) and overall survival (P = 0.0359) in comparison with individuals with weak IL32 tumor expression. This overexpression was negatively correlated with gender (P = 0.0292) and p53 expression (P = 0.0307). In addition, in vitro data linked IL32 expression to metastasis formation since IL32 inhibition decreased Snai1 expression and tumor cell migration in a Boyden chamber assay. Our data provide new insight into the role of IL32 in HNSCC aggressiveness. (c) 2013 Wiley Periodicals, Inc. [less ▲]

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See detailL'addiction au Soleil, son estocade et la parade des crèmes solaires.
FRANCHIMONT, Claudine ULg; Hermanns-Lê, Trinh ULg; PIERARD, Gérald ULg et al

in Revue Médicale de Liège (2013), 68(5-6), 321-325

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See detailThe skin landscape in diabetes mellitus. Focus on dermocosmetic management.
PIERARD, Gérald ULg; Seite, Sophie; Hermanns-Lê, Trinh ULg et al

in Clinical, Cosmetic and Investigational Dermatology (2013), 6

BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening ... [more ▼]

BACKGROUND: Some relationships are established between diabetes mellitus (DM) and a series of cutaneous disorders. Specific dermatoses are markers for undiagnosed DM. Other disorders represent supervening complications in an already treated DM patient. OBJECTIVE: To review the information about dermocosmetic care products and their appropriate use in the management and prevention of dermatoses related to DM. METHOD: The peer-reviewed literature and empiric findings are covered. Owing to the limited clinical evidence available for the use of dermocosmetics, a review of the routine practices and common therapies in DM-related dermatoses was conducted. RESULTS: Some DM-related dermatoses (acanthosis nigricans, pigmented purpuric dermatosis) are markers of macrovascular complications. The same disorders and some others (xerosis, Dupuytren's disease) have been found to be more frequently associated with microangiopathy. Other skin diseases (alopecia areata, vitiligo) were found to be markers of autoimmunity, particularly in type 1 DM. Unsurprisingly, using dermocosmetics and appropriate skin care has shown objective improvements of some DM-related dermatoses, such effects improve the quality of life. The most common skin manifestations of DM fall along continuum between "dry skin," xerosis, and acquired ichthyosis, occurring predominately on the shins and feet. Dermocosmetic products improve the feeling of well-being for DM patients. [less ▲]

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See detailComment j'explore ... l'atteinte fonctionnelle cutanee d'une sclerodermie.
Hermanns-Lê, Trinh ULg; Franchimont, Claudine ULg; PIERARD, Gérald ULg et al

in Revue Médicale de Liège (2013), 68(3), 141-7

Scleroderma refers to distinct clinical presentations sharing in common a sclerotic process most often clinically obvious on the skin. The involvement possibly affects the skin alone in morphea or in ... [more ▼]

Scleroderma refers to distinct clinical presentations sharing in common a sclerotic process most often clinically obvious on the skin. The involvement possibly affects the skin alone in morphea or in combination with internal lesions in systemic sclerosis. Some objective and non-invasive functional assessments are useful for better appreciating the severity and evolution of the disease, as well as to monitor the therapeutic efficacy. In this endeavour, in vivo measurements of the skin mechanical properties are unsurprisingly informative. [less ▲]

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See detailChimiothérapie, immunodépression et cancers secondaires : rapport d'un cas clinique
COLLINS, Patrick ULg; Vijgen, S.; DE PRIJCK, Bernard ULg et al

in Revue Médicale de Liège (2013), 7-8

We report the case of a multi-metastatic mucinous adenocarcinoma of the colon discovered pre-mortem in a patient with a history of multiple myeloma. This case gives the opportunity to discuss the ... [more ▼]

We report the case of a multi-metastatic mucinous adenocarcinoma of the colon discovered pre-mortem in a patient with a history of multiple myeloma. This case gives the opportunity to discuss the prognostic value of histological typing of colorectal cancer and secondary neoplasms to chemotherapy and/or immunodepression. [less ▲]

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See detailNovel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
EL SHAZLY, Amr ULg; Begon, Dominique ULg; KUSTERMANS, Gaëlle ULg et al

in Journal of Biological Chemistry (2013), 288(2), 1374-84

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and ... [more ▼]

We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues, showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase inhibition, or calcium chelation. Western blot demonstrated a novel CRTH2 mediated cytosol to membrane translocation of PKC-epsilon, PKC-delta and PKA-alpha, gamma and IIalpha reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. [less ▲]

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See detailOrganized Proteomic Heterogeneity in Colorectal Cancer Liver Metastases and Implications for Therapies
Turtoi, Andrei ULg; Blomme, Arnaud; Debois, Delphine et al

in Hepatology (Baltimore, Md.) (2013)

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems ... [more ▼]

Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis dis- played increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demon- strate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. Conclusion: The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of target- able antigens. [less ▲]

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See detailImmunohistochemical sweat gland profiles.
Noel, Fanchon; Pierard, Gérald ULg; Delvenne, Philippe ULg et al

in Journal of Cosmetic Dermatology (2013), 12

Abstract BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers ... [more ▼]

Abstract BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. METHODS: This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. RESULTS: The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. CONCLUSION: Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. [less ▲]

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See detailNovel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue
EL SHAZLY, Amr ULg; Castillo-Doloriert, Hugo; Bisig, Bettina et al

Poster (2013)

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed ... [more ▼]

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy.
Objective: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. Methods: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. Results: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. Conclusions and Clinical Relevance: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]

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See detailExpansion of CD16+ CD56+ NK cells in vericyte® NK cell growth medium
Brohée, Laura ULg; Bastin, Renaud ULg; Wingert, S et al

Poster (2013)

Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation ... [more ▼]

Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation receptor such as NKG2D or by inducing Fcγ receptor (FcγRIII, CD16) mediated antibody dependent cellular cytotoxicity (ADCC). Current NK cell-based cancer immunotherapy aims to produce large amounts of functional NK cells, unfortunately most culture media used for NK cell expansion induced the downregulation of CD16 on NK cells. Here, we tested the impact of a new NK cell growth medium (Vericyte® from Medicyte) on CD16 expression. Sorted NK cells and peripheral blood mononuclear cells (PBMC) were cultivated in vericyte® NK cell growth medium and cells issued from these cultures were characterized in term of expansion and phenotype at several time points. After 5 days of culture, an expansion of both NK cells and PBMC was observed and maintained at least until day 20 of culture. In PBMC cultures, we observe only a small preferential NK cell growth since NK cells were around 5-10% at beginning of the culture and this percentage increased to 15% at the end of the culture. However, these cells showed a high proliferative potential when we started the culture with sorted NK cells (the proportion of contaminant cells remain low, under 5%). NK cells expressed CD56 and NKp46 and interestingly after a decreased expression of CD16 on the cell surface at day 3, this receptor was up regulated and most of the cells are CD56bright CD16bright from day 7 to day 12. According FACS FCS/SSC dot plot, NK cells acquired morphology of large activated lymphocytes and some of them expressed activation markers such CD25. Finally, these cells were able to kill efficiently tumour cell line K562. Thus our data show that vericyte® NK cell growth medium allows the expansion of functional CD16+CD56+ NK cells. Cytokine production and ADCC function are under investigation. [less ▲]

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See detailAnalytic dermoscopy of superficial basal cell carcinoma.
FRANCHIMONT, Claudine ULg; Hermanns, Jean-Francois; Caucanas, Marie et al

in Journal of Case Reports in Medicine (2013), 3

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