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1.
Encephale ; 43(4): 363-373, 2017 Aug.
Artigo em Francês | MEDLINE | ID: mdl-27669996

RESUMO

OBJECTIVES: Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. METHODS: We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). RESULTS: Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. CONCLUSIONS: BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/terapia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Ritmo Circadiano , Humanos , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/psicologia
2.
J Struct Biol ; 196(2): 127-137, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26994554

RESUMO

Nacre is able to induce bone-forming cells mineralization, and gains widely interest in bone regeneration. While, the osteoinductive compounds are not yet identified. ESM (Ethanol Soluble Matrix), a nacre extract from powder of Pinctada margaritifera pearl oyster shell, has been firstly proven having the capacity to induce mineralization and to restore mineralization defect in vitro. It is suitable to treat ESM as a source of osteoinductive compounds. Herein, we develop a new method for separating and purifying nacre extracts by an ionic approach. At first, cationic ESM (ESMc) and anionic ESM (ESMa) were achieved with ion-exchange resin. Then, ESM was separated and collected on cation exchange HPLC. Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectrometry (EDS) was used to reveal the concentrated elements in ESM fractions. A coupled cell models were used to test the ESM fractions. Alizarin Red staining was performed and quantified to evaluate the mineralization level. ESMc and 2 HPLC fractions stimulated the mineralization in both cells. EDS demonstrated the abundant presence of calcium and chloride in the osteogenic fractions. To validate, pure CaCl2 was tested and proven having an osteogenic effect in both cells, but less stable than ESM. The mineralization nodules induced by ESM fractions and CaCl2 differed in both cells. In conclusion, a new method was developed for separating and purifying nacre extracts by an ionic approach. By which, the osteoinductive compounds in ESM were proven cationic, and calcium in ESM was demonstrated to play a role in inducing the cell mineralization.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Nácar/química , Nácar/farmacologia , Osteogênese/efeitos dos fármacos , Células 3T3/efeitos dos fármacos , Animais , Cátions , Etanol , Humanos , Camundongos , Nácar/isolamento & purificação , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Pinctada/química
3.
J Struct Biol ; 192(3): 500-509, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26496825

RESUMO

Osteoarthritis (OA) is the most common cause of joint chronic pain and involves the entire joints. Subchondral osteoarthritic osteoblasts present a mineralization defect and, to date, only a few molecules (Vitamin D3 and Bone Morphogenetic Protein2) could improve the mineralization potential of this cell type. In this context, we have tested for the first time the effect of nacre extract on the mineralization capacity of osteoblasts from OA patients. Nacre extract is known to contain osteogenic molecules which have demonstrated their activities notably on the MC3T3 pre-osteoblastic cell line. For this goal, molecules were extracted from nacre (ESM, Ethanol Soluble Matrix) and tested on osteoblasts of the subchondral bone from OA patients undergoing total knee replacement and on MC3T3 cells for comparison. We chose to investigate the mineralization with Alizarin Red staining and with the study of extracellular matrix (ECM) structure and composition. In a complementary way the structure of the ECM secreted during the mineralization phase was investigated using second harmonic generation (SHG). Nacre extract was able to induce the early presence (after 7 days) of precipitated calcium in cells. Raman spectroscopy and electron microscopy showed the presence of nanograins of an early crystalline form of calcium phosphate in OA osteoblasts ECM and hydroxyapatite in MC3T3 ECM. SHG collagen fibers signal was present in both cell types but lower for OA osteoblasts. In conclusion, nacre extract was able to rapidly restore the mineralization capacity of osteoarthritis osteoblasts, therefore confirming the potential of nacre as a source of osteogenic compounds.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Fosfatos de Cálcio/metabolismo , Nácar/farmacologia , Osteoartrite/metabolismo , Osteoblastos/metabolismo , Células 3T3 , Animais , Artroplastia do Joelho , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Durapatita/metabolismo , Matriz Extracelular/metabolismo , Humanos , Camundongos , Microscopia Eletrônica de Varredura , Osteocalcina/biossíntese , Osteopontina/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Análise Espectral Raman
4.
J Clin Pharm Ther ; 39(2): 168-74, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24384030

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The CHOP regimen with rituximab (R-CHOP) remains the standard for chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). The cardiotoxicity of doxorubicin appears to be a key problem in clinical practice. We studied the cardiotoxicity of CHOP/R-CHOP regimen in a retrospective series. The prognostic factors of congestive heart failure (CHF) were investigated, including the impact of empirical cardioprotection by dexrazoxane. METHODS: Patients with an aggressive NHL between 1994 and 2005 were included. Cardiac events were defined as either a decline in resting left ventricular ejection fraction (LVEF) <50%, a decline in LVEF of ≥20% from baseline or as clinical evidence of CHF. The risk of cardiotoxicity was explored by the Kaplan-Meier method. RESULTS: The study included 180 consecutive patients. During the second period of the survey, cardioprotective therapy by dexrazoxane was administered to 45% of patients. The 5-year cumulative risks of cardiac events (29% vs. 8%) and clinical CHF (17% vs. 1·5%) varied significantly between the two periods of study (1994-2000 vs. 2001-2005). In multivariate analysis, use of dexrazoxane (HR = 0·1 [0·01-0·75], P = 0·02) and age  < 60 years (HR = 0·4 [0·17-0·9], P = 0·03) appeared as protective factors of cardiac events. WHAT IS NEW AND CONCLUSION: Our study confirmed the weight of cardiac toxic effect of CHOP ± R regimen. Even if the use of dexrazoxane is highly debatable in curative situations, it may be an effective prevention of cardiotoxicity in aggressive NHL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexrazoxano/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cardiotônicos/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Rituximab , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
5.
Eur Respir J ; 38(1): 98-105, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21406511

RESUMO

The characteristics of residual excessive sleepiness (RES), defined by an Epworth score >10 in adequately treated apnoeic patients, are unknown. 40 apnoeic patients, with (n = 20) and without (n = 20) RES, and 20 healthy controls underwent clinical interviews, cognitive and biological tests, polysomnography, a multiple sleep latency test, and 24-h sleep monitoring. The marked subjective sleepiness in the RES group (mean ± sd score 16.4 ± 3) contrasted with moderately abnormal objective measures of sleepiness (90% of patients with RES had daytime sleep latencies >8 min). Compared with patients without RES, the patients with RES had more fatigue, lower stage N3 percentages, more periodic leg movements (without arousals), lower mean sleep latencies and longer daytime sleep periods. Most neuropsychological dimensions (morning headaches, memory complaints, spatial memory, inattention, apathy, depression, anxiety and lack of self-confidence) were not different between patients with and without RES, but gradually altered from controls to apnoeic patients without and then with RES. RES in apnoeic patients differs markedly from sleepiness in central hypersomnia. The association between RES, periodic leg movements, apathy and depressive mood parallels the post-hypoxic lesions in noradrenaline, dopamine and serotonin systems in animals exposed to intermittent hypoxia.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Fadiga , Feminino , França , Humanos , Hipóxia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polissonografia , Sono , Fases do Sono , Fatores de Tempo
6.
Nat Commun ; 9(1): 1133, 2018 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-29556040

RESUMO

In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination. HDR stimulation by Cas9-HE, however, depends on the guide RNA used, a limitation that may be overcome by testing multiple guides to the locus of interest. The Cas9-HE fusion is simple to use and allows obtaining twofold or more efficient transgene integration than that with Cas9 in several experimental systems, including human cell lines, iPS cells, and rat zygotes.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas Nucleares/metabolismo , Reparo de DNA por Recombinação , Animais , Sequência de Bases , Sistemas CRISPR-Cas , Proteínas de Transporte/química , Proteínas de Transporte/genética , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Endodesoxirribonucleases , Elementos Facilitadores Genéticos , Feminino , Células HCT116 , Células HEK293 , Recombinação Homóloga , Humanos , Mutação INDEL , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Oócitos/metabolismo , Fosforilação , Multimerização Proteica , RNA Guia de Cinetoplastídeos/genética , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transgenes , Integração Viral/genética , Zigoto/metabolismo
7.
Ann Biol Clin (Paris) ; 65(2): 143-52, 2007.
Artigo em Francês | MEDLINE | ID: mdl-17353168

RESUMO

The performances of the images digitalization and teletransmission systems make them more and more used. Applied to cellular haematology, they contribute to confrontations of diagnosis mostly within the framework of therapeutic trials. We present one of the first approaches of the use of telehematology for the inclusion of patients in the Goelams Chronic Lymphocytic Leukaemia 98 trial. The advantages were the constitution of a protected data bank, conveniently consultable; expertise on identical documents; facility of the exchanges between experts. We were able to set new standards of images sampling for CLL, solve the semantic divergences, to point out the inter-observer variability for the morphology. The limiting factors were the personal investment of the experts, but mainly the implication of first line morphologists which should benefit from adequate tools to apprehend this system of second reading like a quality control.


Assuntos
Leucemia Linfoide/imunologia , Leucemia Linfoide/patologia , Telemedicina , Humanos , Imunofenotipagem , Estudos Multicêntricos como Assunto , Variações Dependentes do Observador , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Bone Marrow Transplant ; 38(6): 417-20, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16951691

RESUMO

The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) in patients with newly diagnosed PCNSL. Twenty-five patients received two courses of initial chemotherapy combining methotrexate, etoposide, carmustine and methylprednisolone, and one course of ifosfamide-cytarabine followed by peripheral stem cell collection. Seventeen responsive patients then received HDT using carmustine, etoposide, cytarabine and melphalan with autologous stem cell rescue. After ASCT for responding patients or after salvage therapy for non-responders, whole brain radiation therapy at a dose of 30 Gy was delivered. The objective response rate to the induction chemotherapy was 84%. Four of the 21 responding patients did not have ASCT because of toxicity or refusal. With a median follow-up time of 34 months, the projected event free survival rate is 46% at 4 years. Projected overall survival is 64% at 4 years. Sixteen patients are actually in continuous complete response. No evidence of late treatment-related toxicity was observed. This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Transplante de Células-Tronco , Adulto , Carmustina/administração & dosagem , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Linfoma/mortalidade , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Transplante de Células-Tronco/mortalidade , Transplante Autólogo
10.
Leukemia ; 13(4): 524-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10214857

RESUMO

We prospectively assessed autologous stem cell transplantation for consolidation treatment in a trial of intensive chemotherapy in high risk myelodysplastic syndromes (MDS). In this trial, patients aged 55 years or less with no HLA-identical sibling and achieving CR were scheduled to receive unmanipulated autologous bone marrow transplantation (ABMT) preceded by a consolidation chemotherapy course. Forty-two of the 83 patients aged 55 years or less included in the trial (51%) achieved CR. Three were allografted in CR. Twenty-four of the remaining 39 patients who achieved CR (62%) received ABMT (16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (eight patients). Indeed, as bone marrow harvest was often insufficient, APSCT was subsequently proposed after mobilization by consolidation chemotherapy followed by G-CSF. The conditioning regimen combined cyclophosphamide and busulfan. ABMT and APSCT were performed 1-7 months (median 3) after CR achievement. Hematological reconstitution occurred in all patients and tended to be faster after APSCT than ABMT although not significantly. Three patients died from the procedure, nine relapsed after 2-26 months and 12 (50%) were still in CR after 8-55 months. In autografted patients, median Kaplan-Meier disease-free survival and survival were 29 and 33 months from the autograft, respectively. Thus, ABMT or APSCT can be performed in almost two-thirds of MDS patients who achieve CR with intensive chemotherapy. PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MDS patients autografted in CR. Longer follow-up is required to determine if autograft will prolong CR duration in at least some patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/mortalidade , Bussulfano , Ciclofosfamida , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia/induzido quimicamente , Leucemia/etiologia , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Estudos Prospectivos , Quinina/administração & dosagem , Indução de Remissão , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Autólogo
11.
Transplantation ; 59(1): 151-5, 1995 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-7839420

RESUMO

Graft-versus-host disease (GVHD)* is a frequent complication of allogeneic bone marrow transplantation. The potentially beneficial effect of phototherapy for treatment of cutaneous manifestations of GVHD led us to investigate retrospectively the effect of this therapy in a larger series of patients. Eleven patients with cutaneous GVHD (acute GVHD in 4 patients, chronic lichenoid GVHD in 6 patients, and chronic sclerodermatous GVHD in 1 patient) resistant to standard immunosuppressive drugs were treated with phototherapy. Skin lesions showed a complete clearing in 75% of patients with acute GVHD, and a response rate of 70% was observed in patients with chronic GVHD. No effect of phototherapy was achieved in 3 patients. Our results suggest that phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD, who already take high doses of immunosuppressive drugs.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/terapia , Fototerapia , Dermatopatias/terapia , Adolescente , Adulto , Criança , Doença Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia PUVA , Estudos Retrospectivos
12.
Transplantation ; 60(9): 939-42, 1995 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-7491697

RESUMO

A double-blind, placebo-controlled trial of BT563, including 13 European centers, was initiated in October 1989 to compare the efficacy of the combination of in vivo anti-CD25 mAb (BT 563), cyclosporine, and steroids versus placebo and CSA-steroids in the treatment of grade II and III acute graft-versus-host disease (GVHD). Sixty-nine patients participated in the study, which excluded non-genotypically identical allogeneic bone marrow transplant recipients. No statistically significant differences were observed, clinically or biologically, between the 2 groups before the onset of the treatment. Treatment responses were scored during and after the 3-week treatment period (mAb or placebo). Efficacy was evaluated on days 4, 10, 20, 30, and 60 or on any day the patient's condition was found to be deteriorating. Preceding and systemically untreated GVHD of grade I was observed in 59% of the cases. No statistically clinically significant differences between the 2 groups were observed during or upon completion of treatment in GVHD grade. Nine patients in the placebo group and 6 in the active group were withdrawn of the study. Thirteen of these 15 patients were withdrawn because of failure of GVHD therapy (9 in the placebo group and 4 in the BT563 group). At day 20 after onset of the treatment, the response rate was 63% and 70% for the placebo and BT563 groups, respectively (NS). Probability of survival at 1 year was 59% and 66% (NS) for the placebo and active groups, respectively. In conclusion, despite preliminary promising results in the treatment of steroid-resistant acute GVHD, the role of first-line treatment with an in vivo anti-interleukin-2 receptor mAb remains to be determined.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Medula Óssea/imunologia , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/terapia , Imunossupressores/uso terapêutico , Metilprednisolona/uso terapêutico , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Placebos , Transplante Homólogo
13.
Bone Marrow Transplant ; 21(9): 943-6, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9613789

RESUMO

Two patients with Philadelphia-positive chronic myelogenous leukemia underwent allogeneic bone marrow transplantation from a related HLA mismatched donor (patient 1) or from an unrelated HLA-identical donor (patient 2). Following bone marrow transplantation partial engraftment (patient 1) or graft failure (patient 2) occurred followed by autologous Philadelphia negative hematopoietic recovery either spontaneously (patient 1) or after infusion of autologous bone marrow rescue (patient 2). Neither Philadelphia chromosome, nor bcr-abl rearrangement was detectable by PCR analysis up to 7 years (patient 1) and 9 years (patient 2) post-transplantation. These two observations indicate that sustained engraftment of allogeneic bone marrow stem cells following a myeloablative regimen is not necessary to cure chronic myelogenous leukemia. It is hypothesized that the proliferative advantage of Philadelphia-negative progenitors and the anti-leukemic effect of lymphocytes in the graft have resulted in prolonged remission of the patients.


Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Apolipoproteínas B/genética , Sequência de Bases , Primers do DNA/genética , Reação Enxerto-Hospedeiro , Hematopoese , Células-Tronco Hematopoéticas/patologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Linfócitos/imunologia , Masculino , Reação em Cadeia da Polimerase , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo
14.
Adv Exp Med Biol ; 457: 35-46, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10500778

RESUMO

We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12 mg/m2/d d2-5 + AraC 1 g/m2/12 h d1-5, with (Q+) or without (Q-) quinine (30 mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p = 0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p = 0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Genes MDR , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Quinina/uso terapêutico , Adulto , Idoso , Anemia Refratária com Excesso de Blastos/fisiopatologia , Aberrações Cromossômicas , Citarabina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Síndromes Mielodisplásicas/mortalidade , Fenótipo , Indução de Remissão , Análise de Sobrevida
15.
Presse Med ; 24(1): 23-5, 1995 Jan 07.
Artigo em Francês | MEDLINE | ID: mdl-7899330

RESUMO

During the listeriosis epidemic which occurred in France in the summer 1992, three patients with malignant haematopathies hospitalized in our service contracted the disease. Although the retrospective investigations were hindered by the variable incubation period and the impossibility of examining the foods eaten at the time of infection, there was a high probability that two of the patients had been infected by cooked ham and dairy products at home. The third patient was apparently infected in hospital with well-cooked food found to be contaminated. The hypothesis of coinfection has been raised.


Assuntos
Hospedeiro Imunocomprometido , Leucemia/complicações , Listeriose/etiologia , Linfoma/complicações , Idoso , Feminino , França/epidemiologia , Departamentos Hospitalares , Humanos , Leucemia/imunologia , Listeriose/epidemiologia , Listeriose/transmissão , Linfoma/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Oncogene ; 32(10): 1233-9, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22614012

RESUMO

Evidence that lipocalin 2 (LCN2) is oncogenic has grown in recent years and comes from both animal models and expression analysis from a variety of human cancers. In the intestine, LCN2 is overexpressed in colitis patients and its overexpression is a negative prognostic indicator in colorectal cancer. Functionally, LCN2 has a number of different activities that may contribute to its oncogenic potential, including increasing matrix metalloproteinase activity, control of iron availability and stimulating inflammation. In this report, we examined APCmin intestinal tumorigenesis in an LCN2-deficient background. We found that the loss of LCN2 increased tumor multiplicity specifically in the duodenum, suggesting a potential tumor-suppressive activity. Concurrently, however, LCN2 increased the average small intestinal tumor size particularly in the distal small intestine. We found that this increase was correlated to tumor iron(II) content, suggesting that an iron-scavenging role is important for LCN2 oncogenic activity in the intestine.


Assuntos
Proteínas de Fase Aguda/biossíntese , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Lipocalinas/biossíntese , Proteínas Oncogênicas/biossíntese , Proteínas de Fase Aguda/deficiência , Proteínas de Fase Aguda/genética , Animais , Apoptose/fisiologia , Progressão da Doença , Feminino , Genes APC , Neoplasias Intestinais/genética , Lipocalina-2 , Lipocalinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/deficiência , Proteínas Oncogênicas/genética
17.
Bone Marrow Transplant ; 47(4): 542-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21725374

RESUMO

The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to compare two strategies in previously untreated CLL patients aged <60 years. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP followed by six CHOP courses in every 3 months in those achieving a complete or PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as consolidation after three CHOP courses in case of CR or very good PR. A total of 86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates that frontline high-dose therapy with auto-SCT prolongs PFS but does not translate into a survival advantage in advanced CLL patients in the pre-rituximab era.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Taxa de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Vincristina/efeitos adversos
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