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Céline Gélinas

Publications and source records attributed to Céline Gélinas.

At least 19 recordsLinked to original sources
PubMed2006

Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.

Defective apoptosis renders immortalized epithelial cells highly tumorigenic, but how this is impacted by other common tumor mutations is not known. In apoptosis-defective cells, inhibition of autophagy by AKT activation or by allelic disruption of beclin1 confers sensitivity to metabolic stress by inhibiting an autophagy-dependent survival pathway. While autophagy acts to buffer metabolic stress, the combined impairment of apoptosis and autophagy promotes necrotic cell death in vitro and in vivo. Thus, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth. Thus, autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing death by necrosis.

Animals↗
PubMed2006

Towards an integrated approach for the management of ageing nurses.

AIM: The objective of this study is to provide an overview of the ageing of the nursing workforce and to explore retention strategies centred on the entire professional life and on all age groups. BACKGROUND: The presence of an increasing proportion of ageing workers presents a major challenge to the nursing profession. Evaluation Presentation of theories about the development of a healthy workplace leads to the identification of a framework on which managers can base their management decisions. KEY ISSUES: Examples of incentives relating to the framework are presented which were expressed by both nurses under 50 years of age and those over 50. CONCLUSIONS: Introducing incentives centred on all age groups provides an opportunity to create a healthy workplace for all generations of nurses.

Age Factors↗
PubMed2006

Epstein-Barr virus nuclear antigen 2 trans-activates the cellular antiapoptotic bfl-1 gene by a CBF1/RBPJ kappa-dependent pathway.

The human herpesvirus Epstein-Barr virus (EBV) establishes latency and promotes the long-term survival of its host B cell by targeting the molecular machinery controlling cell fate decisions. The cellular antiapoptotic bfl-1 gene confers protection from apoptosis under conditions of growth factor deprivation when expressed ectopically in an EBV-negative Burkitt's lymphoma-derived cell line (B. D'Souza, M. Rowe, and D. Walls, J. Virol. 74:6652-6658, 2000), and the EBV latent membrane protein 1 (LMP1) and its cellular functional homologue CD40 can both drive bfl-1 via an NF-kappaB-dependent enhancer element in the bfl-1 promoter (B. N. D'Souza, L. C. Edelstein, P. M. Pegman, S. M. Smith, S. T. Loughran, A. Clarke, A. Mehl, M. Rowe, C. Gélinas, and D. Walls, J. Virol. 78:1800-1816, 2004). Here we show that the EBV nuclear antigen 2 (EBNA2) also upregulates bfl-1. EBNA2 trans-activation of bfl-1 requires CBF1 (or RBP-J kappa), a nuclear component of the Notch signaling pathway, and there is an essential role for a core consensus CBF1-binding site on the bfl-1 promoter. trans-activation is dependent on the EBNA2-CBF1 interaction, is modulated by other EBV gene products known to interact with the CBF1 corepressor complex, and does not involve activation of NF-kappaB. bfl-1 expression is induced and maintained at high levels by the EBV growth program in a lymphoblastoid cell line, and withdrawal of either EBNA2 or LMP1 does not lead to a reduction in bfl-1 mRNA levels in this context, whereas the simultaneous loss of both EBV proteins results in a major decrease in bfl-1 expression. These findings are relevant to our understanding of EBV persistence, its role in malignant disease, and the B-cell developmental process.

Antigens, Viral↗
PubMed2006

Validation of the critical-care pain observation tool in adult patients.

BACKGROUND: Little research has been conducted to validate pain assessment tools in critical care, especially for patients who cannot communicate verbally. OBJECTIVE: To validate the Critical-Care Pain Observation Tool. METHODS: A total of 105 cardiac surgery patients in the intensive care unit, recruited in a cardiology health center in Quebec, Canada, participated in the study. Following surgery, 33 of the 105 were evaluated while unconscious and intubated and 99 while conscious and intubated; all 105 were evaluated after extubation. For each of the 3 testing periods, patients were evaluated by using the Critical-Care Pain Observation Tool at rest, during a nociceptive procedure (positioning), and 20 minutes after the procedure, for a total of 9 assessments. Each patient's self-report of pain was obtained while the patient was conscious and intubated and after extubation. RESULTS: The reliability and validity of the Critical-Care Pain Observation Tool were acceptable. Interrater reliability was supported by moderate to high weighted kappa coefficients. For criterion validity, significant associations were found between the patients' self-reports of pain and the scores on the Critical-Care Pain Observation Tool. Discriminant validity was supported by higher scores during positioning (a nociceptive procedure) versus at rest. CONCLUSIONS: The Critical-Care Pain Observation Tool showed that no matter their level of consciousness, critically ill adult patients react to a noxious stimulus by expressing different behaviors that may be associated with pain. Therefore, the tool could be used to assess the effect of various measures for the management of pain.

Cardiac Surgical Procedures↗
PubMed2005

Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells.

Recent studies indicate that natural isothiocyanates, such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) possess strong antitumor activities in vitro and in vivo. The nuclear factor kappa B (NF-kappaB) is believed to play an important role in cancer chemoprevention due to its involvement in tumor cell growth, proliferation, angiogenesis, invasion, apoptosis, and survival. In this study, we investigated the effects and the molecular mechanisms of SFN and PEITC on NF-kappaB transcriptional activation and NF-kappaB-regulated gene expression in human prostate cancer PC-3 C4 cells. Treatment with SFN (20 and 30 microM) and PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells. To further elucidate the mechanism, we utilized the dominant-negative mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (SR-IkappaBalpha). Analogous to treatments with SFN and PEITC, SR-IkappaBalpha also strongly inhibited NF-kappaB transcriptional activity as well as VEGF, cylcin D1, and Bcl-X(L) expression. Furthermore, SFN and PEITC also inhibited the basal and UVC-induced phosphorylation of IkappaBalpha and blocked UVC-induced IkappaBalpha degradation in PC-3 C4 cells. In examining the upstream signaling, we found that the dominant-negative mutant of IKKbeta (dnIKKbeta) possessed inhibitory effects similar to SFN and PEITC on NF-kappaB, VEGF, cylcin D1, Bcl-X(L) as well as IkappaBalpha phosphorylation. In addition, treatment with SFN and PEITC potently inhibited phosphorylation of both IKKbeta and IKKalpha and significantly inhibited the in vitro phosphorylation of IkappaBalpha mediated by IKKbeta. Taken together, these results suggest that the inhibition of SFN and PEITC on NF-kappaB transcriptional activation as well as NF-kappaB-regulated VEGF, cyclin D1, and Bcl-X(L) gene expression is mainly mediated through the inhibition of IKK phosphorylation, particularly IKKbeta, and the inhibition of IkappaBalpha phosphorylation and degradation, as well as the decrease of nuclear translocation of p65 in PC-3 cells.

Anticarcinogenic Agents↗
PubMed2004

Divergent C-terminal transactivation domains of Rel/NF-kappa B proteins are critical determinants of their oncogenic potential in lymphocytes.

rel/nf-kappaB genes are amplified, overexpressed, or constitutively activated in many human hematopoietic tumors; however, the molecular mechanisms by which they contribute to tumorigenesis remain to be determined. Here, we explored the oncogenic potential of cellular Rel/NF-kappaB proteins in vitro and in vivo. We show that overexpression of wild-type mouse and human c-rel genes suffices to malignantly transform primary spleen cells in stringent soft agar assays and produce fatal tumors in vivo. In contrast relA and a constitutively active form of IKKbeta did not. Importantly, a hybrid RelA protein with its C-terminal transactivation domain substituted by that of v-Rel was potently oncogenic in vitro and in vivo. The transactivation domain of v-Rel selectively conferred an oncogenic phenotype upon the Rel homology domain (RHD) of RelA, but not to the more divergent RHDs of p50/NF-kappaB1, p52/NF-kappaB2, or RelB. Collectively, our results highlight important differences in the intrinsic oncogenic activity of mammalian c-Rel and RelA proteins, and indicate that critical determinants of their differential oncogenicity reside in their divergent transactivation domains. These findings provide experimental evidence for a role of mammalian Rel/NF-kappaB factors in leukemia/lymphomagenesis in an in vivo animal model, and are consistent with the implication of c-rel in many human lymphomas.

Adenoviridae↗
PubMed2004

Nuclear factor kappa B-dependent activation of the antiapoptotic bfl-1 gene by the Epstein-Barr virus latent membrane protein 1 and activated CD40 receptor.

Suppression of the cellular apoptotic program by the oncogenic herpesvirus Epstein-Barr virus (EBV) is central to both the establishment of latent infection and the development of EBV-associated malignancies. We have previously shown that expression of the EBV latent membrane protein 1 (LMP1) in Burkitt's lymphoma cell lines leads to increased mRNA levels from the cellular antiapoptotic bfl-1 gene (also known as A1). Furthermore, ectopic expression of Bfl-1 in an EBV-positive cell line exhibiting a latency type 1 infection protects against apoptosis induced by growth factor deprivation (B. N. D'Souza, M. Rowe, and D. Walls, J. Virol. 74:6652-6658, 2000). We now report that LMP1 drives bfl-1 promoter activity through interactions with components of the tumor necrosis factor receptor (TNFR)/CD40 signaling pathway. We present evidence that this process is NF-kappa B dependent, involves the recruitment of TNFR-associated factor 2, and is mediated to a greater extent by the carboxyl-terminal activating region 2 (CTAR2) relative to the CTAR1 domain of LMP1. Activation of CD40 receptor also led to increased bfl-1 mRNA levels and an NF-kappa B-dependent increase in bfl-1 promoter activity in Burkitt's lymphoma-derived cell lines. We have delineated a 95-bp region of the promoter that functions as an LMP1-dependent transcriptional enhancer in this cellular context. This sequence contains a novel NF-kappa B-like binding motif that is essential for transactivation of bfl-1 by LMP1, CD40, and the NF-kappa B subunit protein p65. These findings highlight the role of LMP1 as a mediator of EBV-host cell interactions and may indicate an important route by which it exerts its cellular growth transforming properties.

Animals↗
PubMed2004

Pain assessment and management in critically ill intubated patients: a retrospective study.

BACKGROUND: Little research has been done on pain assessment in critical care, especially in patients who cannot communicate verbally. OBJECTIVES: To describe (1) pain indicators used by nurses and physicians for pain assessment, (2) pain management (pharmacological and nonpharmacological interventions) undertaken by nurses to relieve pain, and (3) pain indicators used for pain reassessment by nurses to verify the effectiveness of pain management in patients who are intubated. METHODS: Medical files from 2 specialized healthcare centers in Quebec City, Quebec, were reviewed. A data collection instrument based on Melzack's theory was developed from existing tools. Pain-related indicators were clustered into nonobservable/subjective (patients' self-reports of pain) and observable/objective (physiological and behavioral) categories. RESULTS: A total of 183 pain episodes in 52 patients who received mechanical ventilation were analyzed. Observable indicators were recorded 97% of the time. Patients' self-reports of pain were recorded only 29% of the time, a practice contradictory to recommendations for pain assessment. Pharmacological interventions were used more often (89% of the time) than nonpharmacological interventions (<25%) for managing pain. Almost 40% of the time, pain was not reassessed after an intervention. For reassessments, observable indicators were recorded 66% of the time; patients self-reports were recorded only 8% of the time. CONCLUSIONS: Pain documentation in medical files is incomplete or inadequate. The lack of a pain assessment tool may contribute to this situation. Research is still needed in the development of tools to enhance pain assessment in critically ill intubated patients.

Analgesics↗
PubMed2003

To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.

During their lifetime, cells encounter many life or death situations that challenge their very own existence. Their survival depends on the interplay within a complex yet precisely orchestrated network of proteins. The Rel/NF-kappaB signaling pathway and the transcription factors that it activates have emerged as critical regulators of the apoptotic response. These proteins are best known for the key roles that they play in normal immune and inflammatory responses, but they are also implicated in the control of cell proliferation, differentiation, apoptosis and oncogenesis. In recent years, there has been remarkable progress in understanding the pathways that activate the Rel/NF-kappaB factors and their role in the cell's decision to either fight or surrender to apoptotic challenge. Whereas NF-kappaB is most commonly involved in suppressing apoptosis by transactivating the expression of antiapoptotic genes, it can promote programmed cell death in response to certain death-inducing signals and in certain cell types. This review surveys our current understanding of the role of NF-kappaB in the apoptotic response and focuses on many developments since this topic was last reviewed in Oncogene 4 years ago. These recent findings shed new light on the activity of NF-kappaB as a critical regulator of apoptosis in the immune, hepatic, epidermal and nervous systems, on the mechanisms through which it operates and on its role in tissue development, homoeostasis and cancer.

Animals↗
PubMed2003

Validation evidence for the French Canadian adaptation of the Multidimensional Fatigue Inventory as a measure of cancer-related fatigue.

Cancer-related fatigue is the most reported symptom among patients with cancer. Researchers in the field of psychooncology have encouraged the development of short instruments, which allow for easier completion by clinical populations while still maintaining solid psychometric properties. The current study examined the validity and reliability of the French Canadian adaptation of the Multidimensional Fatigue Inventory (MFI) among women (n = 277) and men (n = 327) undergoing therapy for breast or prostate cancer, respectively. An exploratory factor analysis of the selected 15-item MFI yielded the following four factors: general/physical, mental, reduced motivation, and reduced activity. This was supported by a confirmatory factor analysis. The reliability, as evaluated by test-retest and Cronbach alpha internal consistency reliability coefficients of the French Canadian shortened MFI, was acceptable. In addition, the four factor-based scores correlated in a theoretically meaningful manner with existing measures of mood disturbance (Profile of Mood States and Hospital Anxiety and Depression Scale), cancer-related stressors (Inventory of Recent Life Experiences), coping with illness (Coping with Health Injuries and Problems Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), and insomnia (Insomnia Severity Index), suggesting good construct, convergent, and concurrent criterion validity. Although further validation is recommended, the results for the French Canadian MFI in assessing cancer-related fatigue in both women and men undergoing cancer treatments showed good psychometric qualities.

Adaptation, Psychological↗
PubMed2003

Mutations in the v-Rel transactivation domain indicate altered phosphorylation and identify a subset of NF-kappaB-regulated cell death inhibitors important for v-Rel transforming activity.

Consistent with the constitutive activation of Rel/NF-kappaB in human hematopoietic tumors, the v-Rel oncoprotein induces aggressive leukemia/lymphomas in animal models. v-Rel is thus a valuable tool to characterize the role of Rel/NF-kappaB in cancer and the mechanisms involved. Prior studies by our group identified a serine-rich domain in v-Rel that was required for biological activity. Here, we investigated the molecular basis for the transformation defect of specific serine mutants. We show that the transforming efficiency of these mutants in primary lymphoid cells is correlated with their ability to mediate kappaB site-dependent transactivation and with specific changes in phosphorylation profiles. Interestingly, coexpression of the death antagonists Bcl-xL and Bcl-2 significantly increased their oncogenicity, whereas other NF-kappaB-regulated death inhibitors showed little or no effect. The fact that a subset of apoptosis inhibitors could rescue v-Rel transactivation mutants suggests that their reduced transcriptional activity may critically affect expression of defined death antagonists essential for oncogenesis. Consistent with this hypothesis, we observed selection for high endogenous expression of Bcl-2-related death antagonists in cells transformed by weakly transforming v-Rel mutants. These results emphasize the need for Rel/NF-kappaB to efficiently activate expression of a subset of antiapoptotic genes from the Bcl-2 family to manifest its oncogenic phenotype.

Animals↗
PubMed2003

NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of apoptosis inhibitor Bfl-1/A1.

Expression of the prosurvival Bcl-2 homologue Bfl-1/A1 is induced by NF-kappa B-activating stimuli, while B and T cells from c-rel knockout mice show an absolute defect in bfl-1/a1 gene activation. Here, we demonstrate NF-kappa B-dependent assembly of an enhanceosome-like complex on the promoter region of bfl-1. Binding of NF-kappa B subunit c-Rel to DNA nucleated the concerted binding of transcription factors AP-1 and C/EBP beta to the 5'-regulatory region of bfl-1. Optimal stability of the complex was dependent on proper orientation and phasing of the NF-kappa B site. Chromatin immunoprecipitation analyses demonstrated that T-cell activation triggers in vivo binding of endogenous c-Rel, c-Jun, C/EBP beta, and HMG-IC to the bfl-1 regulatory region, coincident with selective recruitment of coactivators TAFII250 and p300, SWI/SNF chromatin remodeling factor component BRG-1, and basal transcription factors TATA-binding protein (TBP) and TFIIB, as well as hyperacetylation of histones H3 and H4. These results highlight a critical role for NF-kappa B in bfl-1 transcription and point to the need for a complex and precise regulatory network to control bfl-1 expression. To our knowledge, this is the first demonstration of enhanceosome-mediated regulation of a cell death inhibitor.

Acetylation↗
PubMed2003

Validation of a French Canadian version of the Organizational Policies and Practices (OPP) questionnaire.

Organizational factors are potentially powerful in accounting for work-related chronic disability following a musculoskeletal disorder. This study documents the psychometric qualities of the French Canadian version of the Organizational Policies and Practices questionnaire (OPP) [1] on a population of nurses (N=124). By excluding the two items composing the ergonomic practices factor, a factorial structure identical to that obtained by the OPP's authors is obtained for the disability management policies and practices factor, the people-oriented culture factor and the safety climate factor. The internal consistency coefficients (Cronbach's alpha) are satisfactory while the coefficients intraclass are less than those obtained by the authors in the test-retest. However, the test-retest interval is greater in this study. Consistent relationships are observed between the dimensions of the OPP and three job-related psychosocial indicators: perceived stress, social support and satisfaction. This suggests a good construct validity for the OPP. Although additional validation efforts are recommended, all of the results obtained support the validity and reliability of the French Canadian version of the OPP. This version can be used to examine the importance of organizational aspects in studies on the prevention of chronic disability.

Adult↗
PubMed2003

Intra-abdominal pressure monitoring for critically ill patients.

Increased intra-abdominal pressure (IAP) is associated with a variety of clinical situations and has profound effects, both locally and systemically, that may result in organ dysfunction and failure. If not identified and treated promptly, increased IAP can be fatal. Urinary bladder pressure monitoring is a simple and reliable method of quantifying IAP and is a key factor leading to prompt management and a successful outcome for patients.

Abdomen↗
PubMed2002

Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells.

BACKGROUND: Activation of the NF-kappaB transcription factor has been previously demonstrated in two androgen receptor negative prostate cancer cell lines. We wished to extend this work to additional prostate cancer cells and to characterize the mechanisms responsible for constitutive NF-kappaB activation. METHODS: Electrophoretic mobility shift assays were performed to measure NF-kappaB DNA-binding activity in prostate cancer cell lines, and immunohistochemistry was performed to detect nuclear localization of NF-kappaB in prostate cancer tissues. Western blot analysis was used to study the status of IkappaBalpha. Transient transfection assays were employed to characterize the contributions of IkappaB kinase (IKK), MAPK kinase kinases (MAPKKKs), androgen receptor (AR), and tyrosine phosphorylation to the constitutive activation of NF-kappaB in the prostate cancer cell lines. RESULTS: Constitutive NF-kappaB activity was observed in AR-negative cell lines as well as in the prostate cancer patient samples, but was not present in AR positive cells. A "super-repressor" IkappaBalpha, as well as dominant negative forms of IKKbeta and NF-kappaB-inducing kinase (NIK), and tyrosine kinase inhibition were able to suppress NF-kappaB activity in the cells with constitutive activation. CONCLUSIONS: The constitutive activation of NF-kappaB observed in prostate cancer cells is likely due to a signal transduction pathway involving tyrosine kinases, NIK, and IKK activation.

DNA-Binding Proteins↗