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BACKGROUND: Clinically assisted nutrition and hydration via percutaneous endoscopic gastrostomy (PEG) is a therapeutic option to ameliorate the difficulties associated with enhanced catabolism, weight loss, and dysphagia in Huntington's disease (HD). OBJECTIVES: The objective is to provide insights into demographics, staging (Shoulson-Fahn), complications, weight trajectories, and survival rates in people with HD (pwHD) who underwent PEG. METHODS: This retrospective study included 705 consecutive pwHD who attended our HD clinic between July 2006 and March 2024, of whom 52 underwent PEG. A control group (n = 52), comprising pwHD without PEG, were closely matched for sex, stage, age, CAG length, and disease burden score at PEG. The study was registered as a service evaluation at the National Hospital for Neurology and Neurosurgery. RESULTS: PEG prevalence was 15.0% (n = 52/347) among manifest pwHD: 4.8% (n = 3/62) for Stage 3; 33.3% (n = 16/48) for stage 4; and 44.1% (n = 30/68) for stage 5. Commonest indications were dysphagia, weight loss, and inadequate oral intake. Complications included chest infection, tube dislodgement, and peristomal and skin infections. Modeling of weight trajectories after PEG found no difference between PEG and non-PEG groups. Mortality rate was 34.6% (n = 18/52) in the PEG and 36.5% (n = 19/52) in the non-PEG groups (P = 0.84). Treatment duration (until study endpoint or death) was 3.48 years (interquartile range = 1.71-6.02; range = 0.23-18.8), with 65.4% (n = 34/52) alive at the study endpoint. CONCLUSION: PEG in pwHD at-risk for weight loss may help slow weight loss. Prospective studies are required to strengthen PEG decision-making in pwHD. PEG survival was much longer than other dementias, highlighting the need to consider PEG independently in pwHD.
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Gastrostomía , Enfermedad de Huntington , Humanos , Masculino , Femenino , Gastrostomía/métodos , Gastrostomía/efectos adversos , Enfermedad de Huntington/mortalidad , Enfermedad de Huntington/cirugía , Enfermedad de Huntington/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Trastornos de Deglución/etiología , Centros de Atención Terciaria , Resultado del Tratamiento , Pérdida de Peso , Anciano , Nutrición Enteral/métodosRESUMEN
In a recent study, Wilton and colleagues link activation of the classical complement pathway with corticostriatal synapse loss and cognitive decline in Huntington's disease.1.
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Enfermedad de Huntington , Humanos , Sinapsis/metabolismo , CogniciónRESUMEN
Assisted reproductive technologies (ART) account for 1-6% of births in developed countries. While most children conceived are healthy, increases in birth and genomic imprinting defects have been reported; such abnormal outcomes have been attributed to underlying parental infertility and/or the ART used. Here, we assessed whether paternal genetic and lifestyle factors, that are associated with male infertility and affect the sperm epigenome, can influence ART outcomes. We examined how paternal factors, haploinsufficiency for Dnmt3L, an important co-factor for DNA methylation reactions, and/or diet-induced obesity, in combination with ART (superovulation, in vitro fertilization, embryo culture and embryo transfer), could adversely influence embryo development and DNA methylation patterning in mice. While male mice fed high-fat diets (HFD) gained weight and showed perturbed metabolic health, their sperm DNA methylation was minimally affected by the diet. In contrast, Dnmt3L haploinsufficiency induced a marked loss of DNA methylation in sperm; notably, regions affected were associated with neurodevelopmental pathways and enriched in young retrotransposons, sequences that can have functional consequences in the next generation. Following ART, placental imprinted gene methylation and growth parameters were impacted by one or both paternal factors. For embryos conceived by natural conception, abnormality rates were similar for WT and Dnmt3L+/- fathers. In contrast, paternal Dnmt3L+/- genotype, as compared to WT fathers, resulted in a 3-fold increase in the incidence of morphological abnormalities in embryos generated by ART. Together, the results indicate that embryonic morphological and epigenetic defects associated with ART may be exacerbated in offspring conceived by fathers with sperm epimutations.
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Infertilidad Masculina , Placenta , Niño , Embarazo , Masculino , Humanos , Femenino , Animales , Ratones , Placenta/metabolismo , Incidencia , Semen , Reproducción/genética , Metilación de ADN , Técnicas Reproductivas Asistidas/efectos adversos , Espermatozoides/metabolismo , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , PadreRESUMEN
We report on two patients with secondary cough headache who responded to the cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib and showed an independent temporal course. This case report shows that secondary cough headache can also respond to medical treatment and can respond to a COX-2 inhibitor, not previously reported. As is seen in primary cough headache, the headache disorder can go into natural remission (case 1) while the secondary pathology progresses and conversely, persist once the secondary pathology has resolved (case 2). The course of the headache and that of the secondary pathology do not necessarily correlate. It is, therefore, proposed that any treatment of the secondary pathology is independent to that of the headache. In NSAID-intolerant cases a COX-2 inhibitor can be trialled first line.
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Inhibidores de la Ciclooxigenasa 2 , Cefaleas Primarias , Humanos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Antiinflamatorios no Esteroideos , Etoricoxib , Cefalea , Cefaleas Primarias/tratamiento farmacológicoRESUMEN
Advance care planning (ACP) is a useful tool that benefits adult patients, care providers, and surrogate decision makers, through providing opportunities for patients to consider, express, and formalize their beliefs, preferences, and wishes pertaining to decisions regarding future medical care at a time when they retain decision-making capacity. Early and timely consideration of ACP discussions is paramount in Huntington's disease (HD) given the potential challenges in ascertaining decision-making capacity in the advanced stages of the disease. ACP helps to empower and extend patient autonomy, providing clinicians and surrogate decision makers with reassurance that management is consistent with a patient's expressed wishes. Regular follow up is vital to establish consistency of decisions and wishes. We outline the framework of the dedicated ACP clinic integrated within our HD service to highlight the importance of a patient-centred and tailored care plan that fulfils the patient's expressed goals, preferences, and values.
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Planificación Anticipada de Atención , Enfermedad de Huntington , Adulto , Humanos , Enfermedad de Huntington/terapiaRESUMEN
Chorea can be associated with autoimmune diseases such as antiphospholipid syndrome and has been associated with the isolated presence of antiphospholipid antibodies (aPL). Chorea is a rare neurological manifestation of antiphospholipid syndrome. The pathophysiological mechanisms underlying aPL-related chorea are still debated. One postulated mechanism is aPL or other autoantibody binding to brain-blood vessel endothelium, resulting in endothelial dysfunction secondary to a proinflammatory cascade, with sequalae of inflammation and local microthrombosis. Another postulated mechanism considers immune-mediated attack (aPL or antibasal ganglia antibodies) against specific basal ganglia epitopes. Here, we report a patient with isolated aPL-related chorea that followed a relapsing-remitting course. We highlight the role of brain metabolic imaging with fluorodeoxy glucose positron-emission tomography in the diagnostic workup of chorea and the challenges in the practical management of aPL-related chorea with symptomatic treatments.
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Síndrome Antifosfolípido , Enfermedades Autoinmunes , Corea , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico por imagen , Corea/diagnóstico por imagen , Corea/etiología , Anticuerpos Antifosfolípidos , Enfermedades Autoinmunes/complicaciones , Encéfalo/diagnóstico por imagenRESUMEN
Three south-London hospital trusts undertook a feasibility study, comparing data from 93 patients who received the 14-day adhesive ambulatory electrocardiography (ECG) patch Zio XT with retrospective data from 125 patients referred for 24-hour Holter for cryptogenic stroke and transient ischaemic attack following negative 12-lead ECG. As the ECG patch was fitted the same day as the clinical decision for ambulatory ECG monitoring was made, median time to the patient having the monitor fitted was significantly reduced in all three hospital trusts compared with 24-hour Holter being ordered and fitted. Hospital visits reduced by a median of two for patients receiving Zio XT. This project supports that it is feasible to use a patch as part of routine clinical care with a positive impact on care pathways.
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Indomethacin-responsive headaches encompass a group of disorders which include a subset of the trigeminal autonomic cephalalgias and other paroxysmal, often precipitated primary headaches. Many patients show a rapid therapeutic response to indomethacin, which is limited by intolerability. Etoricoxib and celecoxib, selective inhibitors of cyclo-oxygenase-2 (COX-2), spare gastroduodenal COX-1 activity and are less likely to cause gastrointestinal adverse effects than indomethacin. We report a case series of eight patients, seven who responded to etoricoxib and one patient who responded to celecoxib.
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Trastornos de Cefalalgia , Indometacina , Antiinflamatorios no Esteroideos/farmacología , Celecoxib/efectos adversos , Etoricoxib/uso terapéutico , Cefalea/inducido químicamente , Cefalea/tratamiento farmacológico , Trastornos de Cefalalgia/tratamiento farmacológico , Humanos , Indometacina/efectos adversosRESUMEN
We report a patient who has peripheral demyelination in the form of chronic inflammatory demyelinating polyneuropathy (CIDP) with central demyelination following a relapsing-remitting disease course. The patient developed bilateral sequential optic neuritis predating the diagnosis of CIPD, then developed a profound brainstem syndrome with ataxia, dysarthria, a complex eye movement disorder, visual disturbance and urinary incontinence. Interval imaging fulfilled McDonald criteria for multiple sclerosis (MS) with a right parieto-occipital tumefactive lesion showing contrast enhancement and new lesions in the right temporal white matter and midbrain tegmentum. Oligoclonal bands (OCBs) were matched and serum antibodies against aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) were negative. Genetic sequence analysis and deletion/duplication testing revealed variants of uncertain significance with compound heterozygosity for point mutations in two genes, DYNC1H1 and SH3TC2, which are associated with Charcot-Marie-Tooth (CMT) disease though the patient was negative for known CMT mutations. The patient responded poorly to steroids and regular intravenous immunoglobulin (IVIg) but clinically improved following aggressive immunomodulatory therapy with pulsed steroids and plasmapheresis, followed by Rituximab. Combined central and peripheral demyelination (CCPD) is rare. Autoimmune mechanisms are postulated in the pathogenesis. Whether overlap of central and pe- ripheral demyelination is coincidental or caused by a shared epitope in both the peripheral and central nervous systems still remains to be elucidated. There is no clear therapeutic consensus in the treatment of both central and peripheral demyelination, though immunomodulating treatment strategies may minimise disability and improve prognosis.
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Esclerosis Múltiple , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Acuaporina 4 , Humanos , Glicoproteína Mielina-Oligodendrócito , Nervios Periféricos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico por imagen , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/terapiaRESUMEN
INTRODUCTION: Burn injuries are a debilitating cause of morbidity and mortality associated with the long-term impact of psychological factors on quality of life. Accurate assessment of the differential impact of burn sequelae and anxiety is often complicated by the overlap between psychological and somatic symptoms in burns patients. The Beck Anxiety Inventory (BAI) is one validated psychometric tool for anxiety assessment. The primary objective of this study is to investigate whether utilising the BAI as a tool to assess for anxiety in burns patients is biased due to the confounding of symptoms of anxiety with the physical sequelae of a burn injury. METHODS: This is a single-centre, prospective, cross-sectional study. The study was conducted in accordance with the UK Good Clinical Practice guidelines (CAPP reference number 506). Patients were recruited over a three-month period from November 2016 to February 2017 and were offered a modified BAI questionnaire to complete. Patients were asked to indicate to what degree they attributed each symptom to their physical injury or their psychological state on a visual analogue scale (VAS). RESULTS: 50 patients, comprising 33 females (66%) and 17 males (34%), participated in the study with a median age of 33.5 years (range: 20-88). Date of injury spanned May 1991 to January 2017. Percentage of the total body surface area (% TBSA) affected by burn ranged from 1 to 86%. Patients attributed eight of the 21 self-report items within the BAI as being more physical than psychological in origin. The results reveal a statistical significant difference in patient VAS scores between physical (mean: 34.16, 95% CI: 29.04-39.28) and psychological (mean: 61.2, 95% CI: 56.33-66.17) BAI items, with p<0.0001. In addition, patients with a facial burn injury were more likely to report 'face flushed' (Mann-Whitney U Test, Z=-2.11, p<0.05) and patients with a hand burn injury were more likely to report 'hands trembling' (Mann-Whitney U Test, Z=-2.52, p<0.05). CONCLUSIONS: This feasibility study found preliminary evidence suggesting that the BAI may, in part, represent misattributed symptoms of cutaneous injury from burns. However, whilst our findings suggest an attribution bias, there is not enough evidence from this data to comment on whether its use should be restricted in burns patients. Further research is needed to formally quantify convergent and divergent validity through structured interviews. In addition, further research using other self-report tools of anxiety in burns patients would be useful to corroborate the prospect of biased and confounded anxiety scores.
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Ansiedad/psicología , Quemaduras/psicología , Traumatismos Faciales/psicología , Traumatismos de la Mano/psicología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Sesgo , Superficie Corporal , Quemaduras/fisiopatología , Estudios Transversales , Traumatismos Faciales/fisiopatología , Femenino , Traumatismos de la Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Escala Visual Analógica , Adulto JovenRESUMEN
INTRODUCTION: An investigation into long-term cognitive impairment and Quality of Life (QoL) after severe burns. METHODS: A proof of principle, cohort design, prospective, observational clinical study. Patients with severe burns (>15% TBSA) admitted to Burns ICU for invasive ventilation were recruited for psychocognitive assessment with a convenience sample of age and sex-matched controls. Participants completed psychological and QoL questionnaires, the Cogstate® electronic battery, Hopkins Verbal Learning, Verbal Fluency and Trail making tasks. RESULTS: 15 patients (11M, 4F; 41±14 years; TBSA 38.4%±18.5) and comparators (11M, 4F; 40±13 years) were recruited. Burns patients reported worse QoL (Neuro-QoL Short Form v2, patient 30.1±8.2, control 38.7±3.2, p=0.0004) and cognitive function (patient composite z-score 0.01, IQR -0.11 to 0.33, control 0.13, IQR 0.47-0.73, p=0.02). Compared to estimated premorbid FSIQ, patients dropped an equivalent of 8 IQ points (p=0.002). Cognitive function negatively correlated with burn severity (rBaux score, p=0.04). QoL strongly correlated with depressive symptoms (Rho=-0.67, p=0.009) but not cognitive function. CONCLUSIONS: Severe burns injuries are associated with a significant, global, cognitive deficit. Patients also report worse QoL, depression and post-traumatic stress. Perceived QoL from cognitive impairment was more closely associated with depression than cognitive impairment.
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Atención , Quemaduras/psicología , Disfunción Cognitiva/psicología , Depresión/psicología , Función Ejecutiva , Memoria a Corto Plazo , Recuerdo Mental , Trastornos por Estrés Postraumático/psicología , Adulto , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Cuidados Críticos , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Lenguaje , Masculino , Salud Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Cuestionario de Salud del Paciente , Prueba de Estudio Conceptual , Estudios Prospectivos , Calidad de Vida , Índices de Gravedad del TraumaRESUMEN
This is the first study to ascertain the value of multidisciplinary team (MDT) meetings within an early pregnancy assessment unit (EPAU). Our national telephone survey identified that in the United Kingdom, overall 37% of EPAU utilise regular MDT meetings. Secondary and tertiary hospitals are just as likely to hold regular MDT meetings. The participants in our interview study expressed the principal benefits of regular MDT meetings as communication, education and effective stress management. The perceived additional benefits included improved care quality, better patient experience and enhanced team cohesion. During the meetings, at least, one representative from every tier of staffing was present. The caseload of the MDT meeting comprised ectopic pregnancies and pregnancies of unknown location. We propose a number of research studies, which would build on this study. Such efforts will help enhance the effectiveness of the MDT-based EPAU service.
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Procesos de Grupo , Grupo de Atención al Paciente/organización & administración , Atención Prenatal/organización & administración , Femenino , Humanos , Comunicación Interdisciplinaria , Embarazo , Atención Prenatal/métodos , Evaluación de Programas y Proyectos de Salud , Calidad de la Atención de Salud , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Pharmacological treatments for Tourette syndrome (TS) vary in efficacy between different patients. The evidence base is limited as even high quality controlled studies tend to be of relatively short duration which may lose relevance in clinical usage. Patients are frequently treated with serial agents in the search for efficacy and tolerability. The success of this strategy has not been previously documented. We examined 400 consecutive TS patients seen over a 10-year period, some with a longer prior history in other clinics; 255/400 (64%) were prescribed medication. We present this heterogeneous cohort in terms of the number of drugs they had tried, and as a proxy measure of some benefit of the last drug used, whether it had been prescribed under our supervision for ≥ 5 months. The most commonly prescribed medications were aripiprazole (64%), clonidine (40%), risperidone (30%) and sulpiride (29%) with changes in prescribing practises over the period examined. The number of different drugs tried were one (n = 155), two (n = 69), three (n = 36), four (n = 14), five (n = 15), six (n = 5), seven (n = 2) and eight (n = 1). The data illustrate the difficulty in drug treatment of tics and suggest that even after trials of several agents there is potential benefit in trying further options.
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Antipsicóticos/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tics/tratamiento farmacológico , Síndrome de Tourette/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antipsicóticos/administración & dosificación , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tics/etiología , Síndrome de Tourette/fisiopatología , Adulto JovenRESUMEN
Genome-wide demethylation and remethylation of DNA during early embryogenesis is essential for development. Imprinted germline differentially methylated domains (gDMDs) established by sex-specific methylation in either male or female germ cells, must escape these dynamic changes and sustain precise inheritance of both methylated and unmethylated parental alleles. To identify other, gDMD-like sequences with the same epigenetic inheritance properties, we used a modified embryonic stem (ES) cell line that emulates the early embryonic demethylation and remethylation waves. Transient DNMT1 suppression revealed gDMD-like sequences requiring continuous DNMT1 activity to sustain a highly methylated state. Remethylation of these sequences was also compromised in vivo in a mouse model of transient DNMT1 loss in the preimplantation embryo. These novel regions, possessing heritable epigenetic features similar to imprinted-gDMDs are required for normal physiological and developmental processes and when disrupted are associated with disorders such as cancer and autism spectrum disorders. This study presents new perspectives on DNA methylation heritability during early embryo development that extend beyond conventional imprinted-gDMDs.
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ADN (Citosina-5-)-Metiltransferasas/genética , Genoma Humano , ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , HumanosRESUMEN
BACKGROUND: Epidemiological measures of the prevalence of fetal alcohol spectrum disorders (FASD) vary greatly in the literature. Irrespective of the methodology, the criteria to define a 'case' are set by the researchers. Hence, estimates of the prevalence of FASD primarily depend on the diagnostic criteria currently available. The problem lies therein - the aforementioned criteria are ill-defined. MATERIALS & METHODS: A critical analysis of the diagnostic criteria from the Institute of Medicine, Hoyme, 4-Digit Diagnostic Code and Canadian guidelines was performed, with particular attention focused on the inconsistencies in specificities of the fetal alcohol syndrome (FAS) facial phenotype. RESULTS: To date, the Canadian guidelines represent the only guidelines that have pushed for a uniform diagnostic capacity through harmonizing the IoM and 4-Digit Diagnostic Code criteria. In the absence of a reliable biochemical marker of effect to confirm maternal drinking during pregnancy, the importance and dependence on diagnostic guidelines for FASD is understated. With the availability of four published guidelines for diagnoses across the spectrum of FASD, there is a need to reach a set standard globally. There are profound implications of relaxed and strict diagnostic approaches on FAS prevalence reporting in the literature. CONCLUSIONS: This review exposes the clinical burden of diagnosing the range of FASD with disputing diagnostic criteria. Discrepancies in the criteria pose a danger to the validity of FASD diagnoses with respect to inaccurate estimates of incidence and prevalence. In turn, these discrepancies risk compromising the future healthcare of affected individuals with regards to intervention, counselling and treatment.
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Trastornos del Espectro Alcohólico Fetal/epidemiología , Guías de Práctica Clínica como Asunto , Canadá/epidemiología , Niño , Femenino , Trastornos del Espectro Alcohólico Fetal/diagnóstico , Humanos , Fenotipo , Embarazo , PrevalenciaRESUMEN
PURPOSE: Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow. Despite different options of therapy, Waldenstrom macroglobulinemia is still incurable. Src tyrosine kinase has been shown to play a central role in the regulation of a variety of biological processes, such as cell proliferation, migration, adhesion, and survival in solid tumors. We sought to determine whether the protein tyrosine kinase Src regulates adhesion, migration, and survival in Waldenstrom macroglobulinemia. EXPERIMENTAL DESIGN: We tested the expression of Src tyrosine kinase in Waldenstrom macroglobulinemia and normal cells, and the effect of the specific Src inhibitor AZD0530 on the adhesion, migration, cell cycle, and survival of a Waldenstrom macroglobulinemia cell line and patient samples. Moreover, we tested the effect of AZD0530 on cytoskeletal and cell cycle signaling in Waldenstrom macroglobulinemia. RESULTS: We show that Src is overexpressed in Waldenstrom macroglobulinemia cells compared with control B cells, and that the use of the Src inhibitor AZD0530 led to significant inhibition of adhesion, migration, and cytoskeletal signaling induced by SDF1. Moreover, inhibition of Src activity induced G(1) cell cycle arrest; however, it had minimal effect on survival of Waldenstrom macroglobulinemia cells, and no significant effect on survival of normal cells. CONCLUSIONS: Taken together, these results delineate the role of Src kinase activity in Waldenstrom macroglobulinemia and provide the framework for future clinical trials using Src inhibitors in combination with other drugs to improve the outcome of patients with Waldenstrom macroglobulinemia.
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Quimiotaxis , Proteína Oncogénica pp60(v-src)/fisiología , Macroglobulinemia de Waldenström/patología , Benzodioxoles/farmacología , Adhesión Celular/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quimiocina CXCL12/farmacología , Quimiotaxis/efectos de los fármacos , Citotoxinas/farmacología , Evaluación Preclínica de Medicamentos , Humanos , Proteína Oncogénica pp60(v-src)/antagonistas & inhibidores , Proteína Oncogénica pp60(v-src)/metabolismo , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Macroglobulinemia de Waldenström/metabolismoRESUMEN
Within the past few years, major advances in the preclinical and clinical testing of novel therapeutic agents have occurred in Waldenström's macroglobulinemia (WM). These include agents that target the PI3K/Akt/mTOR pathway, PKC pathways, NF-kB signaling pathway, as well as tyrosine kinases and histone deacetylase inhibitors. In this review, we summarize the current understanding of the clinical development of these agents in WM.
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Antineoplásicos/uso terapéutico , Macroglobulinemia de Waldenström/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , HumanosRESUMEN
The interaction of multiple myeloma (MM) cells with their microenvironment in the bone marrow (BM) provides a protective environment and resistance to therapeutic agents. We hypothesized that disruption of the interaction of MM cells with their BM milieu would lead to their sensitization to therapeutic agents such as bortezomib, melphalan, doxorubicin, and dexamethasone. We report that the CXCR4 inhibitor AMD3100 induces disruption of the interaction of MM cells with the BM reflected by mobilization of MM cells into the circulation in vivo, with kinetics that differed from that of hematopoietic stem cells. AMD3100 enhanced sensitivity of MM cell to multiple therapeutic agents in vitro by disrupting adhesion of MM cells to bone marrow stromal cells (BMSCs). Moreover, AMD3100 increased mobilization of MM cells to the circulation in vivo, increased the ratio of apoptotic circulating MM cells, and enhanced the tumor reduction induced by bortezomib. Mechanistically, AMD3100 significantly inhibited Akt phosphorylation and enhanced poly(ADP-ribose) polymerase (PARP) cleavage as a result of bortezomib, in the presence of BMSCs in coculture. These experiments provide a proof of concept for the use of agents that disrupt interaction with the microenvironment for enhancement of efficacy of cytotoxic agents in cancer therapy.