205 research outputs found
Acute leukemia lymphoblastic in 2015 : contribution of the oncogenic and molecular risk factors to an adapted treatment
No full textLes leucémies aiguës (LA) sont un groupe hétérogène d'hémopathies malignes dues à latransformation oncogénique clonale des cellules souches hématopoïétiques (CSH). On distingue les LA myéloblastiques etlymphoblastiques (LAL). Les LAL sont classées selon le type de précurseur lymphoïde atteint, leur degré de maturité et leurs anomalies cytogénétiques.Le traitement permettant d'obtenir 80 à 90 % de rémission complète (RC) comporte une chimiothérapie d'induction, une consolidation et une intensification(intensification retardée ou allogreffe de CSH selon la situation pronostique). Néanmoins la survie globale à long terme n'est que de 40 à 50 %, du fait de la survenue de rechutes et de la toxicité des traitements. Différents groupes pronostiques basés sur la cytogénétique et la biologie moléculaire se dégagent,pouvant bénéficier de thérapeutiques adaptées. Dans les LAL à chromosome philadelphie (LAL à Ph),antérieurement de mauvais pronostic, les inhibiteurs de tyrosine kinase (ITK) permettent d'obtenir 80% de RCavec cependant un taux de rechute non négligeable. Nous avons démontré qu'une intensification thérapeutique par autogreffe chez des patients avec une maladie résiduelle indétectable permettait une survie à long terme prolongée avec une toxicité moindre que celle de l'allogreffe. En montrant l'implication de l'autotaxine dans les mécanismes de résistance aux ITK dans les LAL à Ph, nous ouvrons la voie à l'utilisation potentielle de nouvelles thérapeutiques. Dans les LAL T, groupe considéré de bon pronostic, un tiers des patients rechute. Nous avons démontré que l'absence de mutation de Notch et/ou FBXW7 ou la présence de mutations de RAS ou PTEN était de mauvais pronostic identifiant un sous-groupe de LAL T dont le traitement devait être renforcé. Nos travaux ont ainsi contribué à l'identification des groupes pronostiques dans les LAL et à l'adaptation des traitements afin d'améliorer les chances de survie.Acute leukemias are a heterogeneous groups of malignant hematological diseases due to the clonaloncogenic transformation of hematopoietic stem cells(HSTs). We distinguish acute myeloblastic leukaemiafrom acute lymphoblastic leukemia (ALL). ALLs are classified according to the type of lymphoid precursoraffected, its degree of maturity, and with associated cytogenetic abnormalities.Treatment incorporating induction therapy,consolidation, and intensification – delayedintensification or allogeneic stem cell transplantation(SCT) according to prognostic factors – enable 80 to 90% of complete remission (CR). Nevertheless, long-termoverall survival is only 40 to 50% because of relapseand treatment-related toxicity. Different prognosticgroups based on cytogenetic abnormalities andmolecular biology are emerging and patients from eachprognostic group can benefit from adapted therapies.In chromosome Philadelphia-positive ALL (Ph+ ALL) which used to be of particular bad prognosis, tyrosinekinase inhibitors (TKIs) enables 80% of CR but with ahigh-relapse risk. We demonstrated that high-dosetherapy followed by autologous SCT enables prolongedlong-term survival with less drug-related toxicity ascompared to allogeneic SCT in patients with undetectable minimal residual disease. By showing the implication of autotaxine in the resistance to TKIs inPh+ LAL, we enable the use of novel therapeutics inclinical practice.T-cell ALL is considered of poor prognosis as one thirdof patients relapse. In this group of patients we showedthat the absence of a Notch and/or a FBXW7 mutation or the presence of mutations in RAS or PTEN identified a subgroup of patients in whom the treatmentmust be intensified. Our research has contributed to the identification of prognostic groups in ALL and to theadjustment of treatment according to potential survival
Développer le dépistage pour réduire les inégalités sociales face aux cancers
No full textInternational audienc
Contribution à l'étude des tumeurs de la tête et du cou (analyse critique de certaines voies d'abord chirurgicales des espaces rétro et latéro-pharyngés et des facteurs pronostiques des lymphomes malins non-hodgkiniens de la tête et du cou)
No full textLes espaces rétro et latéro-pharyngés sont le siège de tumeurs de nature histologique très variée. Leur richesse en éléments lymphatiques les rend particulièrement exposés aux disséminations lymphatiques des carcinomes épidermoïdes mais aussi aux localisations primitives et secondaires des lymphomes malins de la tête et du cou. Leur abord à visée diagnostique ou thérapeutique reste délicat. La première partie de ce travail a permis de préciser la technique, les limites et les indications de trois voies d'abord peu usitées. La voie trans-orale permet l'exérèse de lésions de volume modéré et bien encapsulées de ces espaces avec une très faible morbidité. Les progrès de la chirurgie robotisée devraient permettre d'étendre ses indications. La voie cervico-transmandibulaire procure une parfaite exposition de la base du crâne et un excellent contrôle des éléments vasculo-nerveux qui en sortent. Elle apparaît indiquée pour l'exérèse des volumineuses tumeurs des espaces péripharyngés enchâssées contre la base du crâne, ou qui englobent la carotide interne. La voie infralabyrinthique s'adresse aux lésions du foramen jugulaire à développement essentiellement extra-crânien. Elle permet d'éviter un déroutement du nerf facial et peut, en cas de nécessité, être aisément convertie en une voie d'abord plus large. La deuxième partie de ce travail est consacrée à l'étude des lymphomes malins non hodgkiniens de la tête et du cou. Elle a permis, d'une part, de confirmer la faisabilité et les bons résultats d'un traitement combiné associant chimiothérapie et radiothérapie et, d'autre part, d'affiner les facteurs pronostiques déjà décrits dans le cadre des lymphomes non hodgkiniens quelle que soit leur localisation. Ainsi un âge supérieur à 45ans, une masse tumorale de plus de 5cm, une maladie localisée aux glandes salivaires et l'atteinte de plusieurs sites extra-ganglionnaires se sont révélés être de pronostic défavorable.Various histologic types of tumours can be found in the parapharyngeal spaces. Their access for diagnosis or treatment purpose remains delicate. The first part of this work focused on three rarely used surgical approaches in order to specify their technique, limits and indication. The trans oral route allows surgical removal of well encapsulated lesions of small volume with a low morbidity. The advances in robotic surgery should enlarge its indications. The cervical trans mandibular approach gives an excellent overview on the skull base and on the neuro-vascular structures coming out from it. It appeared to be indicated for removal of voluminous parapharyngeal lesions abutting the skull base or surrounding the internal carotid artery. The infralabyrinthique route concerns tumors of the jugular foramen with an extra cranial development. It avoids a facial nerve diversion and can easily be transformed, if needed, in a larger route. The second part of this work is dedicated to the study of head and neck non Hodgkin lymphomas. It first confirmed the feasibility and the good results of a combine treatment of high dose CHOP regimen and involved field radiotherapy. Secondly it refined the prognostic factors yet described for non Hodgkin lymphoma of any localization. Patient's age > 45 years old, bulky disease (> 5 cm), a disease localized to salivary glands, and multiple extra nodal site involvement were the main predictors of a worse outcome.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF
Foreign Nationals’ Liveability in the Dammam Metropolitan Area Petroleumscape
No full textSince oil was struck at Dammam’s Oil Well No. 7 in 1938, the Dammam Metropolitan Area (henceforth referred to as ‘DMA) has undergone rapid urban expansion, in part due to the influx of foreign national oil workers. With their lifestyles differing from the local population, the urban sphere has developed to cater to their diverse demands. There is limited literature on the relationship between the history the foreign national populations’ urban experiences in the DMA and its petroleumscape. The petroleumscape, as defined by Carola Hein, is the physical, represented and lived palimpsest of petroleum’s physical and financial flows into the (urban) landscape guided by corporate and public actors. In the DMA, the petroleumscape’s main actor - ARAMCO – was the first to define spatial distributions of ethnic and socioeconomic groups in Saudi’s Eastern Province. Other actors such as the Saudi government and other petrochemical companies followed suit, resulting in ethnically segregated urban zones and architectural typologies. A failure to understand the historical relationships between petroleum, ethnicity and nationality could be an obstacle to current Saudi city-planning strategies, particularly frameworks such as Vision 2030, which anticipate an economy slowly shifting away from oil and ‘inclusive’ cities. This paper investigates how the development of the DMA’s petroleumscape resulted in urban spaces for foreign national populations (henceforth referred to as ‘FN populations’) and affected their urban liveability in terms of their housing, work, education and leisure environments. A study of this intricate historical relationship could provide a background for future urban planning policies in the DMA and the Eastern Province of Saudi Arabia. The analysis of historic documents, aerial imagery, photographs and geographical information systems can locate oil-related infrastructure throughout history. Coupled with personal accounts and statistics, segregation and integration of FNs in urban space is explored. An online questionnaire conducted for this research provides quantitative and qualitative data on the quality of life for FNs. Secondary sources, such as books, articles and magazines which investigate housing and employment conditions in Middle Eastern oil and port cities are used to analyse and deduce findings from primary sources. A cross analysis of sources and findings identifies and maps out urban interventions that improve liveability arising from Dammam’s petroleumscape. The historical upward trajectory of Dammam’s petroleum industry has improved liveability for FN residents since the discovery of oil in 1938. Consequently, through the creation of urban spaces, such as gated communities, cultural enclaves and commercial districts funded by petrodollars, liveability for FN populations has improved in tandem with the rise of petroleum. However, a generalisation of all FN groups cannot be made as their urban liveability has historically depended, and continues to depend, on their position on the racial and socioeconomic ladder. Saudi’s waning reliance on oil revenue will affect liveability in the DMA for Saudis and foreign nationals alike, possibly even altering urban distributions of various FN groups. The objective is to present the correlations and causations in the history of the DMA’s urban development and its FN population and to illustrate how and why this affects liveability for FNs so that the objectives of local planning authorities can better manage the demands of a historically diverse population, in line with the Vision 2030 framework and local urban planning schemes.AR2A011Architecture, Urbanism and Building Science
A Trifle Strife?: Public Space, Rituals and Communalism
No full textThis study investigates Bengaluru’s Chamarajpet Eidgah Maidan as a proxy of Hindu-Muslim religious communalism manifesting in public space. The maidan has been a ground of controversy since June 2022 due to a conflict over its use for (religious) ritual activities. The incumbent Hindu-nationalist BJP government fails to mediate such contestations of socio-religious public space between Hindu and Muslim groups. The main risk, among others, is an escalation of communal violence. However, other major risks include the disenfranchisement of Chamarajpet Maidan’s everyday existence, and by extension, of its everyday stakeholders. A failure to understand these tensions will exacerbate the megacity’s existing infrastructural and social woes. This study explores how public space could address religious communalism. It has been found that, in addition to exploring the religious and ritual meanings of the maidan through analytical cartographies, an analysis of its ‘worldings’ - through media representations and physical-social realities - were invaluable to produce a countercartography of the maidan. These countercartographies were possible with reference to books, journal articles, news articles, historical maps, site observations and interviews. Public architecture could address religious communalism if the maidan’s religious conflict is addressed alongside its everyday social needs. A longterm view necessitates the integration of (unanticipated) stakeholder uses and clear governance for infrastructural resilience. Politicised religions, which normalise a Muslim versus Hindu antagonism, is becoming ever more rampant in India. To understand its spatial ramifications is a first step in addressing a nation-wide problem.Architecture, Urbanism and Building Sciences | Transitional Territorie
Contribution à l'étude des tumeurs de la tête et du cou : analyse critique de certaines voies d'abord chirurgicales des espaces rétro et latéro-pharyngés et des facteurs pronostiques des lymphomes malins non-hodgkiniens de la tête et du cou
No full textVarious histologic types of tumours can be found in the parapharyngeal spaces. Their access for diagnosis or treatment purpose remains delicate. The first part of this work focused on three rarely used surgical approaches in order to specify their technique, limits and indication. The trans oral route allows surgical removal of well encapsulated lesions of small volume with a low morbidity. The advances in robotic surgery should enlarge its indications. The cervical trans mandibular approach gives an excellent overview on the skull base and on the neuro-vascular structures coming out from it. It appeared to be indicated for removal of voluminous parapharyngeal lesions abutting the skull base or surrounding the internal carotid artery. The infralabyrinthique route concerns tumors of the jugular foramen with an extra cranial development. It avoids a facial nerve diversion and can easily be transformed, if needed, in a larger route. The second part of this work is dedicated to the study of head and neck non Hodgkin lymphomas. It first confirmed the feasibility and the good results of a combine treatment of high dose CHOP regimen and involved field radiotherapy. Secondly it refined the prognostic factors yet described for non Hodgkin lymphoma of any localization. Patient's age > 45 years old, bulky disease (> 5 cm), a disease localized to salivary glands, and multiple extra nodal site involvement were the main predictors of a worse outcome.Les espaces rétro et latéro-pharyngés sont le siège de tumeurs de nature histologique très variée. Leur richesse en éléments lymphatiques les rend particulièrement exposés aux disséminations lymphatiques des carcinomes épidermoïdes mais aussi aux localisations primitives et secondaires des lymphomes malins de la tête et du cou. Leur abord à visée diagnostique ou thérapeutique reste délicat. La première partie de ce travail a permis de préciser la technique, les limites et les indications de trois voies d'abord peu usitées. La voie trans-orale permet l'exérèse de lésions de volume modéré et bien encapsulées de ces espaces avec une très faible morbidité. Les progrès de la chirurgie robotisée devraient permettre d'étendre ses indications. La voie cervico-transmandibulaire procure une parfaite exposition de la base du crâne et un excellent contrôle des éléments vasculo-nerveux qui en sortent. Elle apparaît indiquée pour l'exérèse des volumineuses tumeurs des espaces péripharyngés enchâssées contre la base du crâne, ou qui englobent la carotide interne. La voie infralabyrinthique s'adresse aux lésions du foramen jugulaire à développement essentiellement extra-crânien. Elle permet d'éviter un déroutement du nerf facial et peut, en cas de nécessité, être aisément convertie en une voie d'abord plus large. La deuxième partie de ce travail est consacrée à l'étude des lymphomes malins non hodgkiniens de la tête et du cou. Elle a permis, d'une part, de confirmer la faisabilité et les bons résultats d'un traitement combiné associant chimiothérapie et radiothérapie et, d'autre part, d'affiner les facteurs pronostiques déjà décrits dans le cadre des lymphomes non hodgkiniens quelle que soit leur localisation. Ainsi un âge supérieur à 45ans, une masse tumorale de plus de 5cm, une maladie localisée aux glandes salivaires et l'atteinte de plusieurs sites extra-ganglionnaires se sont révélés être de pronostic défavorable
The position of the M-BCR breakpoint does not predict the duration of chronic phase or survival in chronic myeloid leukemia
No full textIt has been reported that patients with chronic myeloid leukemia (CML) with 5' breakpoints within the major breakpoint cluster region (M-BCR) of the BCR gene have somewhat better prognoses than those with 3' breakpoints. We studied the position of the breakpoint in 67 patients with CML in chronic phase using conventional Southern blotting. Using restriction enzymes BglII, BamHI and HindIII and two genomic probes, a 0.6 kb (3' M-BCR) probe hybridizing to a part of the intron between exons b3 and b4 and a 2.0 kb (5' M-BCR) probe hybridizing to sequences including exon b1, we localized the breakpoint in M-BCR as occurring 5' (n = 38) or 3' (n = 28) of the HindIII restriction site located just downstream of exon b3. We failed to localize the breakpoint in one patient. The median durations of chronic phase (37 versus 44 months respectively) and of survival (50 versus 51 months respectively) for patients with 5' and 3' breakpoints were not significantly different. When we analysed only patients whose DNA was collected within 4 weeks of diagnosis (5' breakpoints, n = 30; 3' breakpoints, n = 19), there was again no significant difference in duration of chronic phase or survival. The median survivals of patients divided into good, intermediate and poor prognosis categories in accordance with the prognostic index developed by Sokal and colleagues were 54, 50 and 26 months respectively. This study confirms the value of the Sokal prognostic index but provides no support for the notion that the precise genomic position of the breakpoint in M-BCR correlates with prognosis.Journal ArticleFLWNAinfo:eu-repo/semantics/publishe
Contribution à l'étude des tumeurs de la tête et du cou : analyse critique de certaines voies d'abord chirurgicales des espaces rétro et latéro-pharyngés et des facteurs pronostiques des lymphomes malins non-hodgkiniens de la tête et du cou
No full textVarious histologic types of tumours can be found in the parapharyngeal spaces. Their access for diagnosis or treatment purpose remains delicate. The first part of this work focused on three rarely used surgical approaches in order to specify their technique, limits and indication. The trans oral route allows surgical removal of well encapsulated lesions of small volume with a low morbidity. The advances in robotic surgery should enlarge its indications. The cervical trans mandibular approach gives an excellent overview on the skull base and on the neuro-vascular structures coming out from it. It appeared to be indicated for removal of voluminous parapharyngeal lesions abutting the skull base or surrounding the internal carotid artery. The infralabyrinthique route concerns tumors of the jugular foramen with an extra cranial development. It avoids a facial nerve diversion and can easily be transformed, if needed, in a larger route. The second part of this work is dedicated to the study of head and neck non Hodgkin lymphomas. It first confirmed the feasibility and the good results of a combine treatment of high dose CHOP regimen and involved field radiotherapy. Secondly it refined the prognostic factors yet described for non Hodgkin lymphoma of any localization. Patient's age > 45 years old, bulky disease (> 5 cm), a disease localized to salivary glands, and multiple extra nodal site involvement were the main predictors of a worse outcome.Les espaces rétro et latéro-pharyngés sont le siège de tumeurs de nature histologique très variée. Leur richesse en éléments lymphatiques les rend particulièrement exposés aux disséminations lymphatiques des carcinomes épidermoïdes mais aussi aux localisations primitives et secondaires des lymphomes malins de la tête et du cou. Leur abord à visée diagnostique ou thérapeutique reste délicat. La première partie de ce travail a permis de préciser la technique, les limites et les indications de trois voies d'abord peu usitées. La voie trans-orale permet l'exérèse de lésions de volume modéré et bien encapsulées de ces espaces avec une très faible morbidité. Les progrès de la chirurgie robotisée devraient permettre d'étendre ses indications. La voie cervico-transmandibulaire procure une parfaite exposition de la base du crâne et un excellent contrôle des éléments vasculo-nerveux qui en sortent. Elle apparaît indiquée pour l'exérèse des volumineuses tumeurs des espaces péripharyngés enchâssées contre la base du crâne, ou qui englobent la carotide interne. La voie infralabyrinthique s'adresse aux lésions du foramen jugulaire à développement essentiellement extra-crânien. Elle permet d'éviter un déroutement du nerf facial et peut, en cas de nécessité, être aisément convertie en une voie d'abord plus large. La deuxième partie de ce travail est consacrée à l'étude des lymphomes malins non hodgkiniens de la tête et du cou. Elle a permis, d'une part, de confirmer la faisabilité et les bons résultats d'un traitement combiné associant chimiothérapie et radiothérapie et, d'autre part, d'affiner les facteurs pronostiques déjà décrits dans le cadre des lymphomes non hodgkiniens quelle que soit leur localisation. Ainsi un âge supérieur à 45ans, une masse tumorale de plus de 5cm, une maladie localisée aux glandes salivaires et l'atteinte de plusieurs sites extra-ganglionnaires se sont révélés être de pronostic défavorable
International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia
No full textAdults with relapsed/refractory acute lymphoblastic leukemia
have an unfavourable prognosis, which is influenced by disease
and patient characteristics. To further evaluate these characteristics,
a retrospective analysis of 1,706 adult patients with Ph-negative
relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed
between 1990-2013 was conducted using data reflecting the standard
of care from 11 study groups and large centers in Europe and the
United States. Outcomes included complete remission, overall survival,
and realization of stem cell transplantation after salvage treatment. The
overall complete remission rate after first salvage was 40%, ranging
from 35%-41% across disease status categories (primary refractory,
relapsed with or without prior transplant), and was lower after second
(21%) and third or greater (11%) salvage. The overall complete remission
rate was higher for patients diagnosed from 2005 onward (45%,
95% CI: 39%-50%). One- and three-year survival rates after first, second,
and third or greater salvage were 26% and 11%, 18% and 6%, and
15% and 4%, respectively, and rates were 2%-5% higher among
patients diagnosed from 2005. Prognostic factors included younger age,
longer duration of first remission, and lower white blood cell counts at
primary diagnosis. This large dataset can provide detailed reference
outcomes for patients with relapsed/refractory Ph-negative B-precursor
acute lymphoblastic leukemia
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