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1.
Bull Cancer ; 110(11): 1097-1105, 2023 Nov.
Article in French | MEDLINE | ID: mdl-37423830

ABSTRACT

During aging, the onset of mutations at low frequency in hematopoietic cells or clonal hematopoiesis of indeterminate significance favors the evolution towards hemopathies such as myelodysplastic syndromes or acute leukemias, but also cardiovascular diseases and other pathologies. Acute or chronic inflammation related to age influences the clonal evolution and the immune response. Conversely, mutated hematopoietic cells create an inflammatory bone marrow environment facilitating their expansion. Various pathophysiological mechanisms depending on the type of mutation produce the diversity of phenotypes. Identifying factors affecting clonal selection is mandatory to improve patient care.


Subject(s)
Leukemia , Myelodysplastic Syndromes , Humans , Hematopoiesis/genetics , Myelodysplastic Syndromes/genetics , Bone Marrow , Mutation
2.
Musculoskeletal Care ; 21(4): 1098-1104, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37329233

ABSTRACT

BACKGROUND: Psoriatic arthritis (PsA) is a multifaceted inflammatory disease that has a strong negative impact on the quality of life (QoL) of patients. The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire was the first disease-specific patient-derived instrument developed to measure the QoL in patients with PsA. Our objective was to translate the PsAQol into Arabic language and evaluate its reliability and validity in patients with PsA. METHODS: This was a cross-sectional study including patients with PsA. A clinical and biological assessment of the patients was performed at inclusion. The translation of the original PsAQoL into Arabic was performed by a professional bilingual and lay panel. Eight patients were interviewed to assess face and content validity. A separate sample of PsA patients (n = 30) were invited to participate in a test-retest postal study in order to investigate reproducibility and construct validity. One week separated the two administrations. The Arabic version of Health Assessment Questionnaire (HAQ) was used as a comparator instrument for convergent validity. RESULTS: Face and content validity were satisfactory. The Arabic version of the PsAQoL was found to be relevant, understandable and easy to complete in only a few minutes. One item was excluded (item 16). It had no correlation with either the other 19 items or the total score of PsAQol. The Arabic PsAQol had excellent internal consistency (Cronbach's a = 0.926), and test-retest reliability (r = 0.982). There was a positive correlation between the total score of the PsAQoL and the Arabic version of HAQ (Spearman's r = 0.838, p < 10-3 ). Exploratory factor analysis had extracted two factors explaining 55% of the total variance. CONCLUSION: Nineteen items were selected to compose the Arabic version of PsAQoL, which was found to be relevant and understandable and has excellent reliability and construct validity. The new measure will be a valuable new tool for use in routine care for patients' assessment.


Subject(s)
Arthritis, Psoriatic , Quality of Life , Humans , Reproducibility of Results , Cross-Sectional Studies , Surveys and Questionnaires , Language
3.
Hand Surg Rehabil ; 42(4): 337-341, 2023 09.
Article in English | MEDLINE | ID: mdl-37329983

ABSTRACT

The Questionnaire for Patient-Surgeon Relationship (Q-PASREL) is a French "Patient-Reported Experience Measure" for hand surgery patients. It is the only one which considers the impact of the patient-surgeon relationship on time to return to work and cooperation by the surgeon for administrative issues. It has been shown that a good Q-PASREL score is associated with shorter sick leave and faster return to work. To make this instrument available to more countries, we translated the Q-PASREL into six languages (English, Spanish, German, Italian, Arabic and Persian), following a validated "translation and cultural adaptation" process guideline. This process includes multiple forward and backward translations, discussions and reconciliations with final harmonization and cognitive debriefing. For each language, a team was set up, comprising a key in-country hand surgery consultant, native target-language speaker and fluent in French, and several forward and back translators. The final translated versions were reviewed and approved by the project manager. The six versions of Q-PASREL are now available in the appendices of this publication.


Subject(s)
Language , Surgeons , Humans , Translations , Surveys and Questionnaires , Sick Leave
4.
Prog Urol ; 33(1): 21-26, 2023 01.
Article in French | MEDLINE | ID: mdl-36153223

ABSTRACT

INTRODUCTION: The objective of this study was to propose a French version of the satisfaction survey for inflatable penile implant (SSIPI) questionnaire. MATERIAL: Questionnaire validation was performed in three steps: translation into French by two urologists, its validation by the committee of andrologist and sexual medicine (CAMS) and an independent translation in English by another urologist to exclude any distortion with the original version. Furthermore, the questionnaire was tested in few patients having penile implant. RESULTS: The andrology committee approved the French version of the questionnaire. The final version of the questionnaire was successfully tested on all patients. Every patient (n=10) confirmed the good comprehension and pertinence of the questions, and the easy response selection. CONCLUSION: This French version of the SSIPI questionnaire will allow French-speaking urologists to assess the satisfaction of their patients with a penile implant on a large scale. LEVEL OF EVIDENCE: IV.


Subject(s)
Penile Prosthesis , Humans , Patient Satisfaction , Language , Surveys and Questionnaires , Personal Satisfaction , Psychometrics , Reproducibility of Results
5.
Prog Urol ; 32(7): 509-515, 2022 Jul.
Article in French | MEDLINE | ID: mdl-35644729

ABSTRACT

OBJECTIVES: Our work aimed to translate Ditrovie scale into standard Arabic and to verify its validity and reliability in the Tunisian population. MATERIALS: The translation-retro-translation method was the chosen translation method. The committee of experts analyzed these versions and elaborated a pre-final version The Arabic version obtained was conducted on a sample of 100 patients with idiopathic overactive bladder. The reliability of the scale was verified by Cronbach's alpha coefficient and intraclass correlation coefficient. RESULTS: The feasibility and acceptability of the scale was good. The Cronbach's alpha was 0.86. The reproducibility of our scale as well as of each domain were very good (intraclass correlation coefficient>0.9) with a mean of the differences centered and homogeneous in the Bland and Altman graph. CONCLUSION: The standard Arabic version of the Ditrovie scale is a reliable instrument with satisfactory psychometric properties allowing evaluation of quality of life of patients with idiopathic overactive bladder. LEVEL OF EVIDENCE: B.


Subject(s)
Quality of Life , Urinary Bladder, Overactive , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , Translations , Urinary Bladder, Overactive/diagnosis
7.
Rev Epidemiol Sante Publique ; 70(2): 51-58, 2022 Apr.
Article in French | MEDLINE | ID: mdl-35361493

ABSTRACT

BACKGROUND: Patient safety culture (PSC) takes into account a number of individual and organizational factors. Evaluation of PSC with the participation of primary health care professionals can be carried out through self-administered surveys such as the AHRQ's Medical Office Survey on Patient Safety Culture (MOSPSC) questionnaire. AIM: To translate the MOSPSC questionnaire into French, while analyzing its psychometric properties. METHODS: The MOSPSC questionnaire was first translated into French, with linguistic analysis included, and then back-translated into English, in accordance with the ISPOR recommendations. Lastly, the French version of the MOSPSC questionnaire was completed by health professionals from 36 outpatient structures. Study of the psychometric properties (test-retest, Cronbach's α, and factor analysis) was conducted based on the professionals' responses. RESULTS: After linguistic analysis, the notion of "team" was translated in the final questionnaire as "structure". This term was used in the pilot survey of 415 professionals. The participation rate was 64.1% (266/415); 51.9% (138/415) were paramedics (mainly nurses and physiotherapists). The Cronbach coefficient α inclusive of all dimensions was 0.94. A "reporting of safety incidents" dimension was added, and the "staff training" dimension was merged with "development and standardization of office processes", bringing to 13 the number of dimensions identified after factor analysis. CONCLUSIONS: Having been adapted and validated, the French version of the questionnaire can be used as a tool for assessment of PSC in France. It should not only facilitate the monitoring of PSC in primary care facilities, but also prove conducive to comparison of PSC evolution in different establishments. Lastly, it Could contribute to national and international research on risk management in primary care.


Subject(s)
Patient Safety , Safety Management , Health Personnel , Humans , Primary Health Care , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
8.
Rev Epidemiol Sante Publique ; 70(2): 83-89, 2022 Apr.
Article in French | MEDLINE | ID: mdl-35339315

ABSTRACT

OBJECTIVE: The aim of this study was to translate and analyze the psychometric properties of the third version of the Arabic Diabetes Attitude Scale. METHODS: A methodological study of psychometric validation of the scale according to the guidelines of Vallerand cross-cultural validation was conducted. Type 1 and type 2 diabetics, aged 18 and over, without cognitive impairment or altered mental status were recruited on a convenience-sampling basis. An Arabic-language self-administrated developed questionnaire including diabetics' demographic and clinical data and the experimental third version of the Diabetes Attitude Scale was used. All Vallerand cross-cultural validation steps were completed except for convergent validity and confirmatory analysis. RESULTS: A sample of 333 diabetics was recruited. Reliability and validity of the experimental version of the scale were satisfactory. Correlations between test and retest dimensions were close to 1, and overall Cronbach's alpha coefficient of the experimental version was 0.769. The content validity index was 0.82 proving the accuracy of the concept measurements by the scale. Principal components analysis, by orthogonal Varimax rotation, produced nine factors. Correlation coefficients between the five dimensions of the theoretical model of the scale ranged from 0.002 to 0.367, confirming that each dimension measured a single content. CONCLUSION: The third version of the Arabic Diabetes Attitude Scale has been proven valid and reliable. It is ready for use in clinical practice.


Subject(s)
Diabetes Mellitus , Language , Adolescent , Adult , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
9.
Prog Urol ; 31(16): 1090-1092, 2021 Dec.
Article in French | MEDLINE | ID: mdl-34210602

ABSTRACT

INTRODUCTION: The objective of this study was to propose a French version of the Index of Sexual Satisfaction (ISS). MATERIAL AND METHOD: The translation from English to French of the ISS was performed independently by three pediatric surgeons whose mother tongue is French. Then, an English speaker, fluent in French, who was unaware of the original questionnaire, translated the reconciled French version of the ISS into English. RESULTS: The final French version was successfully tested on 25 French-speaking volunteers. CONCLUSION: We present a validated translation of the Sexual Satisfaction Index.


Subject(s)
Orgasm , Translations , Child , Humans , Linguistics , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
10.
J Fr Ophtalmol ; 44(8): 1211-1215, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34281759

ABSTRACT

INTRODUCTION: The goal of our study was to create a cross-cultural adaptation of the questionnaire « National Eye Institute Visual Function Questionnaire ¼ (NEI-VFQ-25) for the Tunisian population (Tu-VFQ-25) and to test its psychometric properties in a group of patients with chronic uveitis. PATIENTS AND METHODS: The study consisted of two steps. The first was translation of the NEI-VFQ-25 and its cross-cultural adaptation to the Tunisian dialect (Tu-VFQ-25) according to the guidelines of Beaton et al. The second step consisted of studying the psychometric properties of the Tu-VFQ-25. Enrolled patients, diagnosed with chronic uveitis, were interviewed face-to-face by two different investigators, followed by a telephone interview by the first investigator 48hours later. Feasibility, internal consistency and reproducibility of the Tu-VFQ-25 were then tested using statistical methods. RESULTS: The mean time taken to administrate the questionnaire to each of the 45 patients was 11min 40 s (± 2min 24 s). Internal consistency was acceptable, with Cronbach's alpha coefficients above 0.7 except the "Ocular Pain" and "Driving" subscales (0.645 and 0.559 respectively). Inter-observer reliability was excellent, with intra-class correlation coefficients (ICC) ranging from 0.857 to 0.985 for all subscales. Test-retest reliability, assessed for 43 patients, was good to excellent, with ICC above 0.80 for all subscales except "General Vision," which had a value of 0.786. CONCLUSION: As with previous versions, the Tu-VFQ-25 is an easy and reliable tool for assessing vision-related quality of life of Tunisian patients with chronic uveitis.


Subject(s)
National Eye Institute (U.S.) , Quality of Life , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , United States
11.
Can J Occup Ther ; 88(2): 108-116, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33653168

ABSTRACT

BACKGROUND.: Occupational therapy's conceptual tools need to be considered from Global South perspectives to make them more culturally relevant and safe. PURPOSE.: This paper uses an empirical example, and the author's professional and academic experiences, to analyze the strengths, limitations, and potential refinement of the Critical Thinking Tool (CTT) and the Participatory Occupational Justice Framework (POJF). KEY ISSUES.: The paper describes processes of critical reflexivity and intercultural translation to compare concepts used in the CTT and POJF with the findings of a study about olive growing in Palestine to consider the applicability of these tools in Global South settings. The CTT should be amended to address collective occupations, and global and historical contexts, and the POJF should embed intercultural translations and solidarity into its philosophy and processes. IMPLICATIONS.: These refinements would enhance the cultural safety of the CTT and the POJF. Tools in occupational therapy will benefit from more evidence to enhance their global utility in an increasingly interconnected world, in which occupational therapists share the duty to tackle social and occupational injustices.


Subject(s)
Occupational Therapy , Humans , Occupations , Philosophy , Social Justice
12.
Rev. bras. psicanál ; 55(1): 25-40, jan.-mar. 2021.
Article in Portuguese | LILACS-Express | LILACS, Index Psychology - journals | ID: biblio-1288965

ABSTRACT

O in-fans, aquele que não pode falar, precisa de alguém que fale por ele, principalmente um psicanalista, para que possa ouvir novamente a linguagem "silenciosa" que se expressa no tempo do Jetztzeit. Através de uma reflexão acerca do trabalho de Freud sobre a afasia e de sua troca de cartas com Fliess, é possível identificar uma prévia importante, que consiste em uma espécie de pré-semiótica, assim como uma hipótese sobre a memória. Além disso, história, sociologia, semiótica e neurociência são interlocutores necessários para o desenvolvimento do tema "o infantil" na psicanálise.


The "in-fans", who cannot speak, needs a narrator, especially a psychoanalyst in the transference, in order to be able to hear again the "silent" language that is expressed in the time of the Jetztzeit. Through a reflection on Freud's work on aphasias and his exchange of letters with Fliess, it is possible to identify important previews which constitute a sort of pre-semiotics, as well as a theory on memory. In addition, history, sociology, semiotics and the neurosciences are all necessary interlocutors for developing the issue of "the infantile" in psychoanalysis.


El in-fans, aquel que no puede hablar, necesita de alguien que hable por él, principalmente un psicoanalista, para que pueda oír nuevamente el lenguaje "silencioso" que se expresa en el tiempo del Jetztzeit. Por medio de una reflexión acerca del trabajo de Freud sobre la afasia y su intercambio de cartas con Fliess, es posible identificar una previa importante, que consiste en una especie de semiótica previa, así como una hipótesis sobre la memoria. Además de ello, historia, sociología, semiótica y neurociencia son interlocutores necesarios para el desarrollo del tema "lo infantil" en psicoanálisis.


L'« in-fans ¼, celui que ne peut pas parler, a besoin d'un narrateur dans le transfert, en spécial un psychanalyste, pour pouvoir entendre à nouveau le langage « silencieux ¼ qui était employée au temps du Jetztzeit. Par le moyen d'une réflexion sur l'Œuvre de Freud concernant les aphasies et son échange de lettres avec Fliess, il est possible d'identifier des prévisions importantes constituant une espèce de pré-sémiotique, aussi bien qu'une théorie de la mémoire. En plus, l'histoire, la sociologie, la sémiotique et les neurosciences sont toutes des interlocutrices nécessaires au développement de ce sujet : « l'infantile ¼ en psychanalyse.

13.
Can J Psychiatry ; 66(3): 306-312, 2021 03.
Article in English | MEDLINE | ID: mdl-32799647

ABSTRACT

OBJECTIF: Disposer d'outils de dépistage valides pour évaluer le trouble de la personnalité limite est essentiel en pratique clinique et en recherche. Parmi les outils existants, le questionnaire sur la personnalité limite (BPQ) présente plusieurs qualités. Cependant, il n'existe pas de version française et il n'a pas été validé avec des adultes dans un échantillon clinique. Les objectifs de cette étude étaient : 1) traduire le BPQ en français; 2) mesurer la validité convergente, prédictive et discriminante, la cohérence interne et la fidélité test-retest. MÉTHODE: Les recommandations de Streiner, Norman et Cairney (2014) sur la traduction d'évaluations ont été suivies. Quarante adultes référés à un programme spécialisé en troubles de la personnalité ont participé à l'étude. Pour évaluer la validité du BPQ français, le questionnaire SCID-II (entrevue et auto-évaluation) fut administré et le diagnostic psychiatrique fut établi par un psychiatre à l'insu. RÉSULTATS: Aucune modification majeure n'a été apportée au BPQ français. Les analyses ont montré une cohérence interne élevée (α = 0,84), une bonne fidélité test-retest (r = 0,77), une discrimination significative avec le trouble de la personnalité schizotypique (r = -0,31; p < 0,05), une convergence significative avec le SCID-II (r = 0,72) et une validité prédictive significative du diagnostic psychiatrique (p < 0,01). CONCLUSIONS: La version française du BPQ présente des qualités psychométriques prometteuses à un usage auprès des personnes ayant un trouble de la personnalité limite.


Subject(s)
Personality , Humans , Surveys and Questionnaires
14.
Can J Aging ; 40(2): 321-330, 2021 06.
Article in English | MEDLINE | ID: mdl-32616105

ABSTRACT

One third of older adults in Canada are foreign-born, yet there is a dearth of literature on this population. When our team set out to engage in a mixed-methods study on the physical activity and mobility of foreign-born older adults (FBOAs), we found limited guidance. The objective of this Research Note is to share the lessons that we learned in implementing a mixed-methods study in five languages, with 49 visible minority FBOAs from diverse ethno-cultural groups. With an emphasis on practical implementation, here we share our reflections on early community engagement, linguistic accessibility and literacy considerations, facilitating communication with the research team, creating a support role for multilingual family members, organisational suggestions, and working with interpreters and monolingual transcribers. The older Canadian population is projected to become increasingly diverse in the coming decades, and it is our hope that this note will further facilitate research in this understudied area.


Subject(s)
Language , Multilingualism , Aged , Canada , Communication , Exercise , Humans
15.
Arch Pediatr ; 27(7): 362-367, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32891481

ABSTRACT

BACKGROUND: Newborns in neonatology are exposed to invasive and painful procedures. The absence of parents during procedures revealed significantly high pain scores. OBJECTIVE: The aim of this study was to assess practices regarding the role of parents during painful and invasive procedures. METHODS: This was a prospective, observational, multicenter study in France in which 471 caregivers participated. Professional practices regarding the role of parents during painful procedures on their child were assessed. Univariate and multivariate analyses were performed to identify factors associated with parental presence during painful procedures. RESULTS: Parental presence was most often allowed during capillary blood sampling, nasogastric tube insertions, and vein punctures, whereas it was mostly restricted during central line insertions, extubations, lumbar punctures, and intubations. However, we found discrepancies depending on the type of facility and caregiver seniority. CONCLUSION: An important variability in practices concerning the role of parents during painful and invasive procedures on their child was reported.


Subject(s)
Healthcare Disparities/statistics & numerical data , Intensive Care, Neonatal/methods , Pain Management/methods , Pain, Procedural/therapy , Parents , Practice Patterns, Nurses'/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Female , France , Humans , Infant, Newborn , Intensive Care, Neonatal/statistics & numerical data , Male , Pain Management/statistics & numerical data , Pain, Procedural/psychology , Parent-Child Relations , Professional-Family Relations , Prospective Studies , Self Report
16.
Genome ; 63(6): 291-305, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32406757

ABSTRACT

Biological conclusions based on DNA barcoding and metabarcoding analyses can be strongly influenced by the methods utilized for data generation and curation, leading to varying levels of success in the separation of biological variation from experimental error. The 5' region of cytochrome c oxidase subunit I (COI-5P) is the most common barcode gene for animals, with conserved structure and function that allows for biologically informed error identification. Here, we present coil ( https://CRAN.R-project.org/package=coil ), an R package for the pre-processing and frameshift error assessment of COI-5P animal barcode and metabarcode sequence data. The package contains functions for placement of barcodes into a common reading frame, accurate translation of sequences to amino acids, and highlighting insertion and deletion errors. The analysis of 10 000 barcode sequences of varying quality demonstrated how coil can place barcode sequences in reading frame and distinguish sequences containing indel errors from error-free sequences with greater than 97.5% accuracy. Package limitations were tested through the analysis of COI-5P sequences from the plant and fungal kingdoms as well as the analysis of potential contaminants: nuclear mitochondrial pseudogenes and Wolbachia COI-5P sequences. Results demonstrated that coil is a strong technical error identification method but is not reliable for detecting all biological contaminants.


Subject(s)
DNA Barcoding, Taxonomic/methods , Electron Transport Complex IV/genetics , Phylogeny , Pseudogenes/genetics , Animals , DNA, Mitochondrial/genetics , Frameshift Mutation/genetics , Humans
17.
Hand Surg Rehabil ; 39(4): 310-315, 2020 09.
Article in English | MEDLINE | ID: mdl-32088423

ABSTRACT

Splinting how the hand can be used in daily life. Therefore, earlier splint removal is thought to improve functional recovery. The aim of our study was to assess the outcomes of patients who removed their splint and started using their hand earlier and compare them to patients who received routine care. Patients with tendon repairs were divided into two groups: Group 1 (Early) started daily use of their hand at the 5th postoperative week and Group 2 (Later) at the 6th week. Patients received regular therapy consisting of an early motion protocol. Assessments were performed at three consecutive time points. Grip and pinch strength was measured and Nine-Hole Peg Test (9HPT) was performed. Disabilities of the Arm, Shoulder and Hand (DASH) and Tampa Scale for Kinesiophobia (TSK) were filled out. Both within-group and between-group analyses were performed. A total of 58 patients with flexor or extensor tendon repairs were analyzed. All parameters improved significantly over time within both groups (P<0.05). When the time effect was ignored, kinesiophobia, disability and functional results - except grip strength - were statistically better in Group 2 group than in Group 1 (P<0.05). Our results showed that, despite the clinically observed recovery, earlier splint removal and start of daily hand use did not truly improve the functional results. To us, this means that the remarkable advances in surgical techniques do not accelerate the physiological healing process. Therefore, clinical recommendations should always be supported with evidence-based data.


Subject(s)
Splints , Tendon Injuries/rehabilitation , Tendon Injuries/surgery , Adult , Disability Evaluation , Exercise Therapy , Fear , Female , Hand Strength , Humans , Male , Recovery of Function , Time Factors
18.
Biochem Cell Biol ; 98(4): 502-510, 2020 08.
Article in English | MEDLINE | ID: mdl-32008367

ABSTRACT

The natural product pateamineA (PatA) is a highly potent antiproliferative agent. PatA and the simplified analog desmethyl, desamino pateamineA (DMDAPatA) have exhibited cytotoxicity selective for rapidly proliferating cells, and have been shown to inhibit cap-dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A) of the eIF4F complex. PatA and DMDAPatA are both known to stimulate the RNA-dependent ATPase, and ATP-dependent RNA helicase activities of eIF4A. The impact of other eIF4F components, eIF4E and eIF4G, on DMDAPatA action were investigated in vitro and in cultured mammalian cells. The perturbation of the eIF4A-eIF4G association was found to be eIF4E- and mRNA cap-dependent. An inhibitory effect on helicase activity of eIF4A was observed when it was part of a complex that mimicked the eIF4F complex. We propose a model of action for DMDAPatA (and by supposition PatA) where the cellular activity of the compound is dependent on an "active" eIF4F complex.


Subject(s)
Adenosine Triphosphatases/metabolism , Epoxy Compounds/chemistry , Epoxy Compounds/pharmacology , Eukaryotic Initiation Factor-4A/antagonists & inhibitors , Macrolides/chemistry , Macrolides/pharmacology , Neoplasms/drug therapy , RNA, Messenger/metabolism , Thiazoles/chemistry , Thiazoles/pharmacology , Adenosine Triphosphatases/genetics , Biological Products , Cell Line , Cell Proliferation , Humans , Neoplasms/metabolism , Neoplasms/pathology , RNA, Messenger/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism
19.
Biochem Cell Biol ; 98(1): 23-30, 2020 02.
Article in English | MEDLINE | ID: mdl-31150585

ABSTRACT

Over the past two decades, the importance of small non-coding RNAs (sncRNAs) as regulatory molecules has become apparent in all three domains of life (archaea, bacteria, eukaryotes). In fact, sncRNAs play an important role in the control of gene expression at both the transcriptional and the post-transcriptional level, with crucial roles in fine-tuning cell responses during internal and external stress. Multiple pathways for sncRNA biogenesis and diverse mechanisms of regulation have been reported, and although biogenesis and mechanisms of sncRNAs in prokaryotes and eukaryotes are different, remarkable similarities exist. Here, we briefly review and compare the major sncRNA classes that act post-transcriptionally, and focus on recent discoveries regarding the ribosome as a target of regulation and the conservation of these mechanisms between prokaryotes and eukaryotes.


Subject(s)
Archaea/genetics , Bacteria/genetics , Eukaryota/genetics , RNA, Small Untranslated/metabolism , Humans , RNA Processing, Post-Transcriptional , RNA, Small Untranslated/genetics , Ribosomes/metabolism
20.
Biochem Cell Biol ; 98(6): 647-652, 2020 12.
Article in English | MEDLINE | ID: mdl-31671279

ABSTRACT

Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumour stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies - namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We have previously demonstrated in established GBM cell lines that eukaryotic initiation factor 5B (eIF5B) promotes the translation of pro-survival and anti-apoptotic proteins. Consequently, silencing eIF5B sensitizes these cells to TRAIL-induced apoptosis. However, established cell lines do not always recapitulate the features of human glioma. Therefore, we investigated this mechanism in patient-derived BTSCs. We show that silencing eIF5B leads to increased TMZ sensitivity in two BTSC lines: BT25 and BT48. Depletion of eIF5B decreases the levels of anti-apoptotic proteins in BT48 and sensitizes these cells to TMZ-induced activation of caspase-3, cleavage of PARP, and apoptosis. We suggest that eIF5B represents a rational target to sensitize GBM tumors to the current standard-of-care.


Subject(s)
Apoptosis/drug effects , Brain Neoplasms/metabolism , Eukaryotic Initiation Factors/metabolism , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/metabolism , Temozolomide/pharmacology , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Eukaryotic Initiation Factors/genetics , Humans , Neoplasm Proteins/genetics , Neoplastic Stem Cells/pathology
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