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1.
AIDS Behav ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836986

RESUMEN

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.

2.
Cancer ; 127(12): 2015-2024, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33739457

RESUMEN

BACKGROUND: Azacitidine (AZA) is the standard treatment for myelodysplastic syndromes (MDS); however, many patients prematurely stop therapy and have a dismal outcome. METHODS: The authors analyzed outcomes after AZA treatment for 402 MDS patients consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche, and they evaluated the North American MDS Consortium scoring system in a clinical practice setting. RESULTS: At treatment discontinuation, 20.3% of the patients were still responding to AZA, 35.4% of the cases had primary resistance, and 44.3% developed adaptive resistance. Overall survival (OS) was better for patients who discontinued treatment while in response because of planned allogeneic hematopoietic stem cell transplantation (HSCT; median OS, not reached) in comparison with patients with primary resistance (median OS, 4 months) or adaptive resistance (median OS, 5 months) or patients responsive but noncompliant/intolerant to AZA (median OS, 4 months; P = .004). After AZA discontinuation, 309 patients (77%) received best supportive care (BSC), 60 (15%) received active treatments, and 33 (8%) received HSCT. HSCT was associated with a significant survival advantage, regardless of the response to AZA. The North American MDS Consortium scoring system was evaluable in 278 of the 402 cases: patients at high risk had worse OS than patients at low risk (3 and 7 months, respectively; P < .001). The score was predictive of survival both in patients receiving BSC (median OS, 2 months for high-risk patients vs 5 months for low-risk patients) and in patients being actively treated (median OS, 8 months for high-risk patients vs 16 months for low-risk patients; P < .001), including transplant patients. CONCLUSIONS: Real-life data confirm that this prognostic scoring system for MDS patients failing a hypomethylating agent seems to be a useful tool for optimal prognostic stratification and for choosing a second-line treatment after AZA discontinuation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Antimetabolitos Antineoplásicos , Azacitidina , Humanos , Síndromes Mielodisplásicos/terapia , América del Norte , Resultado del Tratamiento
3.
FASEB J ; 34(3): 4512-4526, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32027412

RESUMEN

The dentate gyrus of the hippocampus is one of two brain areas generating throughout life new neurons, which contribute to the formation of episodic/associative memories. During aging, the production of new neurons decreases and a cognitive decline occurs. Dietary factors influence neuronal function and synaptic plasticity; among them the phenolic compound hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. As age impacts primarily on the hippocampus-dependent cognitive processes, we wondered whether HTyr could stimulate hippocampal neurogenesis in vivo in adult and aged wild-type mice as well as in the B-cell translocation 1 gene (Btg1) knockout mouse model of accelerated neural aging. We found that treatment with HTyr activates neurogenesis in the dentate gyrus of adult, aged, and Btg1-null mice, by increasing survival of new neurons and decreasing apoptosis. Notably, however, in the aged and Btg1-null dentate gyrus, HTyr treatment also stimulates the proliferation of stem and progenitor cells, whereas in the adult dentate gyrus HTyr lacks any proliferative effect. Moreover, the new neurons generated in aged mice after HTyr treatment are recruited to existing circuits, as shown by the increase of BrdU+ /c-fos+ neurons. Finally, HTyr treatment also reduces the markers of aging lipofuscin and Iba1. Overall, our findings indicate that HTyr treatment counteracts neurogenesis decline during aging.


Asunto(s)
Giro Dentado/citología , Células-Madre Neurales/citología , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Genotipaje , Hipocampo/citología , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Plasticidad Neuronal/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacos , Alcohol Feniletílico/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismo
4.
Dermatol Ther ; 34(1): e14660, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33301216

RESUMEN

Psoriasis is a chronic immune-mediated disease characterized by inflammation of skin (psoriasis) or joints (psoriatic arthritis) or both, resulting from a dysregulation in particular of the T helper (Th)17 functions. There is no available cure for psoriasis, and a life-long treatment is needed to control signs and symptoms. Research interest is high around the newest biological drugs approved for the treatment of moderate to severe psoriasis and psoriatic arthritis, and especially drugs blocking the IL-23/IL-17 axis. Our aim is to review the new biological drugs for the treatment of psoriasis and their adverse effects, focusing on the risk of infections.


Asunto(s)
Artritis Psoriásica , Productos Biológicos/uso terapéutico , Psoriasis , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/efectos adversos , Humanos , Inflamación , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Piel
5.
Dermatol Ther ; 33(1): e13180, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31770477

RESUMEN

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.


Asunto(s)
Infecciones por VIH/complicaciones , Melanoma/patología , Neoplasias Cutáneas/patología , Humanos , Inmunoterapia/métodos , Incidencia , Melanoma/epidemiología , Melanoma/terapia , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/terapia , Tasa de Supervivencia
6.
Eur J Public Health ; 30(3): 551-556, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31598638

RESUMEN

BACKGROUND: Vitamin D is a hot topic in the scientific community. Its deficiency and the implications for the children's health became increasingly discussed during the last 20 years. The main aim of this retrospective study was to determinate the prevalence of vitamin D metabolism disorders in a population of adopted children and their risk factors. METHODS: We gathered data from 2140 children observed in five different National Working Group for the Migrant Children of the Italian Society of Pediatrics centers, variously located in Italy. Serum 25-hydroxy (OH)-D concentration was used to determine every child's vitamin D status, defined as severely deficient (serum 25-OH-D < 10 ng/ml), moderately deficient (serum 25-OH-D {≥10 ng/ml U < 20 ng/ml}), mildly deficient (serum 25-OH-D {≥20 ng/ml U < 30 ng/ml}) and normal (serum 25-OH-D ≥ 30 ng/ml). RESULTS: Mean value of serum 25-OH-D was 22.7 ng/ml (SD ± 12.1). Vitamin D status was deemed as normal in 483 (22.6%) children, mildly deficient in 718 (33.6%) children, moderately deficient in 730 (34.1%) children and severely deficient in 209 (9.8%) children. CONCLUSIONS: A very high percentage of migrant children is affected by hypovitaminosis D, with a strong association with age, geographic origin, season of blood sample collection and time spent in Italy after the arrival. This finding highlights the need for corrective measures. However, these measures cannot be applied without increasing the access of migrant populations to healthcare services.


Asunto(s)
Migrantes , Deficiencia de Vitamina D , Niño , Estudios Transversales , Humanos , Italia/epidemiología , Estudios Retrospectivos , Vitamina D , Deficiencia de Vitamina D/epidemiología
7.
Int J Mol Sci ; 21(8)2020 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-32331450

RESUMEN

Resveratrol (3,5,4'-trihydroxystilbene) is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Resveratrol/farmacología , Resveratrol/uso terapéutico , Animales , Antineoplásicos Fitogénicos/química , Enfermedades Cardiovasculares/tratamiento farmacológico , Fenómenos Químicos , Estudios Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Interacciones Farmacológicas , Humanos , Relación Estructura-Actividad , Investigación Biomédica Traslacional , Resultado del Tratamiento
8.
Dermatol Ther ; 32(2): e12806, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30588732

RESUMEN

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4+ T-cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case-reports, small case-series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.


Asunto(s)
Infecciones por VIH/complicaciones , Inmunosupresores/uso terapéutico , Psoriasis/etiología , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunosupresores/efectos adversos , Psoriasis/epidemiología , Psoriasis/terapia , Calidad de Vida , Índice de Severidad de la Enfermedad
9.
New Microbiol ; 42(1): 43-48, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30957869

RESUMEN

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58±42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/ Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.


Asunto(s)
Brucella melitensis , Brucelosis , Brotes de Enfermedades , Animales , Brucelosis/complicaciones , Brucelosis/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Farmacorresistencia Bacteriana , Humanos , Estudios Retrospectivos , Factores de Riesgo , Sicilia
10.
Eur J Clin Microbiol Infect Dis ; 37(3): 381-390, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29344839

RESUMEN

Most of the effects and complications of cytomegalovirus (CMV) infection are still unknown, even though its tropism for the endothelium has been extensively investigated. In fact, CMV is suspected to be a cause of venous thrombo-embolism (VTE) since 1974, but there is still no consensus about the management of CMV-related thrombosis and how to prevent it. Cytomegalovirus-related thrombosis has been reported mostly in immunocompromised patients, rarely in immunocompetent individuals. In order to identify potential risk factors of CMV-related thrombosis, we performed a systematic review of the literature regarding immunocompetent patients with cytomegalovirus infection and thrombosis. We found 115 cases with a mean age of 37.36 years (SD ± 16.43 years). Almost half the female patients were assuming EP contraception at the time of the event, and almost half the patients were affected by a coagulation disorder. Interestingly, just two women and four men had no risk factor for thrombosis other than the CMV infection at the time of the event. In conclusion, coagulation disorders and EP contraception have to be taken into a great deal of consideration in patients with CMV infection, since they could be important risk factors for VTE. Knowing the correlation with coagulation disorders, the use of anticoagulation drugs cannot be considered overtreatment. It was not feasible to determine the usefulness of an antiviral treatment. Further studies, even randomized ones, are required to determine the usefulness of antiviral drugs and the real prevalence of CMV-related VTE.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Tromboembolia Venosa , Adulto , Comorbilidad , Anticonceptivos Hormonales Orales , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/epidemiología , Adulto Joven
11.
New Microbiol ; 41(4)2018 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-30311622

RESUMEN

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58 ± 42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

12.
Fetal Pediatr Pathol ; 37(5): 337-347, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30260729

RESUMEN

BACKGROUND: Growing evidence suggests that vitamin D deficiency might be implicated in the development of active tuberculosis (TB). We evaluated vitamin D levels in children with active TB compared to children with latent TB infection (LTBI), non-TB pneumonia (NTBP) and healthy controls to determine if there was a difference. METHODS: In this prospective study, vitamin D levels were measured and compared between the four groups and adjusted for age, ethnicity, gender and season of sample collection. RESULTS: Fifty-seven children were included: 24.6% active TB, 28.1% LTBI, 22.8% NPTB and 24.6% healthy controls. 36.8% of all children tested had an insufficient or deficient vitamin D level. Vitamin D level was significantly lower in active TB compared to other groups (p = 0.004). CONCLUSIONS: Our study showed a correlation between hypovitaminosis D and active pulmonary TB.


Asunto(s)
Tuberculosis Latente/sangre , Neumonía/sangre , Tuberculosis/sangre , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones
13.
Dev Biol ; 408(1): 109-25, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26524254

RESUMEN

Cerebellar granule neurons develop postnatally from cerebellar granule precursors (GCPs), which are located in the external granule layer (EGL) where they massively proliferate. Thereafter, GCPs become postmitotic, migrate inward to form the internal granule layer (IGL), further differentiate and form synapses with Purkinje cell dendrites. We previously showed that the Btg family gene, Tis21/Btg2, is required for normal GCP migration. Here we investigated the role in cerebellar development of the related gene, Btg1, which regulates stem cell quiescence in adult neurogenic niches, and is expressed in the cerebellum. Knockout of Btg1 in mice caused a major increase of the proliferation of the GCPs in the EGL, whose thickness increased, remaining hyperplastic even after postnatal day 14, when the EGL is normally reduced to a few GCP layers. This was accompanied by a slight decrease of differentiation and migration of the GCPs and increase of apoptosis. The GCPs of double Btg1/Tis21-null mice presented combined major defects of proliferation and migration outside the EGL, indicating that each gene plays unique and crucial roles in cerebellar development. Remarkably, these developmental defects lead to a permanent increase of the adult cerebellar volume in Btg1-null and double mutant mice, and to impairment in all mutants, including Tis21-null, of the cerebellum-dependent motor coordination. Gain- and loss-of-function strategies in a GCP cell line revealed that Btg1 regulates the proliferation of GCPs selectively through cyclin D1. Thus, Btg1 plays a critical role for cerebellar maturation and function.


Asunto(s)
Cerebelo/crecimiento & desarrollo , Cerebelo/fisiopatología , Ciclina D1/metabolismo , Actividad Motora , Proteínas de Neoplasias/genética , Envejecimiento/metabolismo , Animales , Animales Recién Nacidos , Apoptosis , Recuento de Células , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Cerebelo/patología , Puntos de Control de la Fase G1 del Ciclo Celular , Eliminación de Gen , Humanos , Proteínas Inmediatas-Precoces/metabolismo , Meduloblastoma/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Neoplasias/deficiencia , Proteínas de Neoplasias/metabolismo , Proteínas Supresoras de Tumor/metabolismo
14.
Int J Gynecol Cancer ; 26(9): 1615-1623, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27779546

RESUMEN

BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.


Asunto(s)
Adhesión a Directriz/estadística & datos numéricos , Neoplasias Ováricas/terapia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad
15.
J Cell Physiol ; 230(12): 2881-90, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25967096

RESUMEN

The PC3/Tis21/Btg2 and Btg1 genes are transcriptional cofactors belonging to the Btg/Tob family, which regulate the development of several cell types, including neural precursors. We summarize here the actions of these genes on neural precursors in the adult neurogenic niches and the cognitive defects associated when their expression is altered. We consider also recent findings implicating them in neural and non-neural tumors, since common developmental mechanisms are involved. PC3/Tis21 is required for the regulation of the maturation of stem and progenitor cells in the adult dentate gyrus and subventricular zone (SVZ), by controlling both their exit from the cell cycle and the ensuing terminal differentiation. Such actions are effected by regulating the expression of several genes, including cyclin D1, BMP4, Id3. In cerebellar precursors, however, PC3/Tis21 regulates chiefly their migration rather than proliferation or differentiation, with important implications for the onset of medulloblastoma, the cerebellar tumor. In fact PC3/Tis21 is a medulloblastoma-suppressor, as its overexpression in cerebellar precursors inhibits this tumor; PC3/Tis21 shows anti-tumor activity also in non-neural tumors. Btg1 presents a different functional profile, as it controls proliferation in adult stem/progenitor cells of dentate gyrus and SVZ, where is required to maintain their self-renewal and quiescence, but is apparently devoid of a direct control of their terminal differentiation or migration. Notably, physical exercise in Btg1-null mice rescues the loss of proliferative capability occurring in older stem cells. Both genes could be further investigated as therapeutical targets, namely, Btg1 in the process of aging and PC3/Tis21 as a tumor-suppressor.


Asunto(s)
Encéfalo/metabolismo , Células-Madre Neurales/metabolismo , Neurogénesis , Factores de Transcripción/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Ciclo Celular , Regulación del Desarrollo de la Expresión Génica , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Madre Neurales/patología , Transducción de Señal , Factores de Transcripción/genética , Transcripción Genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
16.
Blood ; 122(23): 3759-66, 2013 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-24085766

RESUMEN

We assessed the prognostic value of minimal residual disease (MRD) within the ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the role of rituximab maintenance in elderly follicular lymphoma (FL) patients after a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to the Euro-MRD consortium, using qualitative and quantitative polymerase chain reactions (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8 subsequent times. Of the 675 expected follow-up samples, 83% were analyzed. Conversion to PCR negativity predicted better progression-free survival (PFS) at all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007). MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36-7.07). MRD is a powerful independent outcome predictor in FL patients who receive rituximab-intensive programs, suggesting a need to investigate its value for decision-making. This trial was registered at www.clinicaltrial.gov as #NCT01144364.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Linfoma Folicular/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Quimioterapia de Consolidación , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Neoplasia Residual , Proteínas de Fusión Oncogénica/genética , Pronóstico , Rituximab
17.
Stem Cells ; 32(7): 1968-82, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24604711

RESUMEN

Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis.


Asunto(s)
Células-Madre Neurales/fisiología , Neurogénesis , Carrera/fisiología , Animales , Ciclo Celular , Células Cultivadas , Hipocampo/citología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Neoplasias/genética
20.
Brain Pathol ; : e13283, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946128

RESUMEN

The prognosis for many pediatric brain tumors, including cerebellar medulloblastoma (MB), remains dismal but there is promise in new therapies. We have previously generated a mouse model developing spontaneous MB at high frequency, Ptch1+/-/Tis21-/-. In this model, reproducing human tumorigenesis, we identified the decline of the Cxcl3 chemokine in cerebellar granule cell precursors (GCPs) as responsible for a migration defect, which causes GCPs to stay longer in the proliferative area rather than differentiate and migrate internally, making them targets of transforming insults. We demonstrated that 4-week Cxcl3 infusion in cerebella of 1-month-old mice, at the initial stage of MB formation, forces preneoplastic GCPs (pGCPs) to leave lesions and differentiate, with a complete suppression of MB development. In this study, we sought to verify the effect of 4-week Cxcl3 treatment in 3-month-old Ptch1+/-/Tis21-/- mice, when MB lesions are at an advanced, irreversible stage. We found that Cxcl3 treatment reduces tumor volumes by sevenfold and stimulates the migration and differentiation of pGCPs from the lesion to the internal cerebellar layers. We also tested whether the pro-migratory action of Cxcl3 favors metastases formation, by xenografting DAOY human MB cells in the cerebellum of immunosuppressed mice. We showed that DAOY cells express the Cxcl3 receptor, Cxcr2, and that Cxcl3 triggers their migration. However, Cxcl3 did not significantly affect the frequency of metastases or the growth of DAOY-generated MBs. Finally, we mapped the expression of the Cxcr2 receptor in human MBs, by evaluating a well-characterized series of 52 human MBs belonging to different MB molecular subgroups. We found that Cxcr2 was variably expressed in all MB subgroups, suggesting that Cxcl3 could be used for therapy of different MBs.

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